TLR-Activated B Cells Suppress T Cell-Mediated Autoimmunity

Lampropoulou, Vicky; Hoehlig, Kai; Roch, Toralf; Neves, Patricia; Gómez, Elisabeth Calderón; Sweenie, Claire H; Hao, Yi; Freitas, Antonio A; Steinhoff, Ulrich; Anderton, Stephen M; Fillatreau, Simon

doi:10.4049/jimmunol.180.7.4763

Cited by 436T-cell and B-cell ImmunologyImmune Response and InflammationMultiple Sclerosis Research Studies

TLR-Activated B Cells Suppress T Cell-Mediated Autoimmunity

Lampropoulou, Vicky, Hoehlig, Kai, Roch, Toralf, Neves, Patricia, Gómez, Elisabeth Calderón, Sweenie, Claire H, Hao, Yi, Freitas, Antonio A +3 more·2008·The Journal of Immunology

DOI 10.4049/jimmunol.180.7.4763

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Abstract

TLR sense microbial infections, and control activation of immune responses. Dendritic cells, macrophages, and B lymphocytes express TLR and the TLR-signaling adaptor protein MyD88. The impact of TLR-activated B cells on T cell-mediated inflammation is unknown. In this study, we have used mice carrying B cell-restricted deficiencies in MyD88 or in distinct TLR to examine the impact of TLR-activated B cells on a T cell-mediated autoimmune disease, experimental autoimmune encephalomyelitis (EAE). We demonstrate that TLR-signaling in B cells suppresses inflammatory T cell responses (both Th1 and Th17), and stimulates recovery from EAE. Only certain TLR are required on B cells for resolution of EAE, and these are dispensable for disease initiation, indicating that a category of TLR agonists preferentially triggers a suppressive function in B cells and thereby limits autoimmune disease. The TLR agonists controlling the regulatory function of B cells are provided by components of Mycobacterium tuberculosis present in the adjuvant. Thus, MyD88 signaling in B cells antagonizes MyD88 signaling in other cells, which drives differentiation of Th17 cells and is required for induction of EAE. Altogether, our data indicate that B cells link recognition of microbial products via TLR to suppression of a T cell-mediated autoimmune disease.

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Bregs are B cells with regulatory and immunosuppressive functions that maintain immunological homeostasis by producing IL-10, IL-35, and TGFβ, thereby suppressing immunopathology.
“Bregs is a generic term used to define B cells endowed with regulatory and immunosuppressive functions. They play a crucial role in maintain ing immunological homeostasis by producing anti-inflammatory cyto kines such as interleukin-10 (IL-10), IL-35, and transforming growth factor-beta (TGFβ ), thereby suppressing immunopathology.”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [58]
Breg differentiation is influenced by signals such as CD40 ligation, TLR stimulation, and cytokine exposure.
“Their differentiation is influenced by signals such as CD40 ligation, TLR stimulation, and cytokine exposure [58,63,64].”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [58]
Bregs inhibit the expansion of pathogenic T cells and other pro-inflammatory immune cells, thereby preventing excessive immune activation.
“Bregs inhibit the expansion of pathogenic T cells and other pro-inflammatory immune cells, thereby preventing excessive immune activation [55 -58].”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [58]

Innate immune recognition
Janeway, C. A., & Medzhitov, R. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.083001.084359 · Cited by 8,394 · cited 1× · see citing works
“TLR have conserved key functions in vertebrates’ innate immune system (13).”
Background
Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in Tlr4 Gene
Poltorak, A., He, X., Smirnova, I., Liu, M.-Y., Huffel, C. V., Du, X., Birdwell, D., Alejos, E., Silva, M., Galanos, C., et al. (1998) · Science · doi:10.1126/science.282.5396.2085 · Cited by 7,631 · cited 1× · see citing works
“Mammals possess at least 12 TLR that provide a powerful system to detect a broad range of pathogens including bacteria (2), mycobacteria (3), viruses (4), fungi (5), and helminths (6).”
Background
Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells
Bettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T. B., Oukka, M., Weiner, H. L., & Kuchroo, V. K. (2006) · Nature · doi:10.1038/nature04753 · Cited by 6,992 · cited 16× · see citing works
“IF N - γ (n g/ m l) MOG(35-55) (μg/ml) 0 20 30 40 10 0 20 40 50”
BackgroundMethodInfluential
A human homologue of the Drosophila Toll protein signals activation of adaptive immunity
Medzhitov, R., Preston-Hurlburt, P., & Janeway, C. A. J. (1997) · Nature · doi:10.1038/41131 · Cited by 6,137 · cited 3× · see citing works
“Following TLR stimulation, they up-regulate costimulatory molecules essential for T cell activation (1), and secrete cytokines releasing primed T cells from the suppressive effect of regulatory T cells (22).”
Background
A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17
Park, H., Li, Z., Yang, X. O., Chang, S. H., Nurieva, R., Wang, Y.-H., Wang, Y., Hood, L., Zhu, Z., Tian, Q., et al. (2005) · Nature Immunology · doi:10.1038/ni1261 · Cited by 4,265 · cited 15× · see citing works
“IF N - γ (n g/ m l) MOG(35-55) (μg/ml) 0 20 30 40 10 0 20 40 50”
BackgroundMethodInfluential
Recognition of Commensal Microflora by Toll-Like Receptors Is Required for Intestinal Homeostasis
Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaneh, F., Edberg, S., & Medzhitov, R. (2004) · Cell · doi:10.1016/j.cell.2004.07.002 · Cited by 4,251 · cited 16× · see citing works
“IF N - γ (n g/ m l) MOG(35-55) (μg/ml) 0 20 30 40 10 0 20 40 50”
BackgroundMethodInfluential
Approaching the asymptote? Evolution and revolution in immunology.Preprint
Janeway, C. (1989) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1989.054.01.003 · Cited by 3,396 · cited 1× · see citing works
“Engagement of TLR can provide the accessory signals needed for activation of effective adaptive immune responses (1, 19, 20).”
Background
The effect of infections on susceptibility to autoimmune and allergic diseases.
Bach, J. (2002) · New England Journal of Medicine · doi:10.1056/nejmra020100 · Cited by 2,714 · cited 1× · see citing works
“Our data provide support for the “hygiene hypothesis”, which relates the sharp increase in incidence of autoimmune disorders (such as MS, type 1 diabetes, or inflammatory bowel disease) in western countries during the last 50 years to the concomitant reduction in incidence of certain infectious diseases (80).”
Result
CpG Motifs in Bacterial DNA and Their Immune Effects
Krieg, A. Μ. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.100301.064842 · Cited by 2,570 · cited 1× · see citing works
“stimulate DC and macrophages, but fail to stimulate B cells, while type B(K) CpG oligonucleotides efficiently activate B cells (64).”
Background
Toll Pathway-Dependent Blockade of CD4+CD25+ T Cell-Mediated Suppression by Dendritic Cells
Pasare, C., & Medzhitov, R. (2003) · Science · doi:10.1126/science.1078231 · Cited by 2,327 · cited 3× · see citing works
“Following TLR stimulation, they up-regulate costimulatory molecules essential for T cell activation (1), and secrete cytokines releasing primed T cells from the suppressive effect of regulatory T cells (22).”
Background
Subsets of Human Dendritic Cell Precursors Express Different Toll-like Receptors and Respond to Different Microbial Antigens
Kadowaki, N., Ho, S., Antonenko, S., de Waal Malefyt, R., Kastelein, R. A., Bazan, F., & Liu, Y.-J. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.6.863 · Cited by 1,964 · cited 1× · see citing works
“Similarly, distinct DC subsets express different repertoires of TLR (66, 67).”
Background
IL-21 initiates an alternative pathway to induce proinflammatory TH17 cells
Korn, T., Bettelli, E., Gao, W., Awasthi, A., Jäger, A., Strom, T. B., Oukka, M., & Kuchroo, V. K. (2007) · Nature · doi:10.1038/nature05970 · Cited by 1,841 · cited 16× · see citing works
“IF N - γ (n g/ m l) MOG(35-55) (μg/ml) 0 20 30 40 10 0 20 40 50”
BackgroundMethodInfluential
A Theory of Self-Nonself Discrimination
Bretscher, P., & Cohn, M. (1970) · Science · doi:10.1126/science.169.3950.1042 · Cited by 1,755 · cited 1× · see citing works
“Engagement of TLR can provide the accessory signals needed for activation of effective adaptive immune responses (1, 19, 20).”
Background
B cells regulate autoimmunity by provision of IL-10
Fillatreau, S., Sweenie, C. H., McGeachy, M. J., Gray, D., & Anderton, S. M. (2002) · Nature Immunology · doi:10.1038/ni833 · Cited by 1,647 · cited 21× · see citing works
“The cells were cultured for a further 24 h before developing the cytokine ELISA with an anti-cytokine detection Ab as previously described (36).”
BackgroundMethodInfluentialSelf-citation
TGF-β and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain TH-17 cell–mediated pathology
McGeachy, M. J., Bak-Jensen, K. S., Chen, Y., Tato, C. M., Blumenschein, W., McClanahan, T., & Cua, D. J. (2007) · Nature Immunology · doi:10.1038/ni1539 · Cited by 1,520 · cited 16× · see citing works
“IF N - γ (n g/ m l) MOG(35-55) (μg/ml) 0 20 30 40 10 0 20 40 50”
BackgroundMethodInfluential
Receptor-Dependent Mechanisms of Cell Stimulation by Bacterial Endotoxin
Ulevitch, R. J., & Tobias, P. S. (1995) · Annual Review of Immunology · doi:10.1146/annurev.iy.13.040195.002253 · Cited by 1,442 · cited 1× · see citing works
“Furthermore, TLR-activated macrophages secrete inflammatory cytokines driving formation of granuloma (15), which limits dissemination of the microbe, and also produce effector substances directly associated with microbe killing (16).”
Background
Cutting Edge: TLR2-Deficient and MyD88-Deficient Mice Are Highly Susceptible to Staphylococcus aureus Infection1
Takeuchi, O., Hoshino, K., & Akira, S. (2000) · Journal of Immunology · doi:10.4049/jimmunol.165.10.5392 · Cited by 1,156 · cited 1× · see citing works
“Mice lacking the TLR-signaling adaptor protein MyD88 show impaired survival upon infections with Staphylococcus aureus (8), Salmonella typhimurium (9), Toxoplasma gondii (10), or Mycobacterium tuberculosis (11), as a result of defects in both innate and adaptive immune defense mechanisms.”
Background
Visualization of peptide-specific T cell immunity and peripheral tolerance induction in vivo.
Kearney, E. R., Pape, K., Loh, D., & Jenkins, M. (1994) · Immunity · doi:10.1016/1074-7613(94)90084-1 · Cited by 1,126 · cited 1× · see citing works
“For instance, TLR agonists can be used as adjuvant to induce strong activation of Ag-reactive T cells, while delivery of the same Ag in saline induces tolerance (21).”
Background
Toll-like Receptor 7 and TLR9 Dictate Autoantibody Specificity and Have Opposing Inflammatory and Regulatory Roles in a Murine Model of Lupus
Christensen, S. R., Shupe, J., Nickerson, K., Kashgarian, M., Flavell, R. A., & Shlomchik, M. J. (2006) · Immunity · doi:10.1016/j.immuni.2006.07.013 · Cited by 1,090 · cited 1× · see citing works
“Deletion of tlr-9 worsens SLE in lupus-prone mice (33, 34), and polymorphisms in tlr-9 gene leading to lower TLR-9 expression can increase predisposition to SLE in human (35).”
Background
Regulation of Phagosome Maturation by Signals from Toll-Like Receptors
Blander, J. M., & Medzhitov, R. (2004) · Science · doi:10.1126/science.1096158 · Cited by 991 · cited 1× · see citing works
“TLR stimulation increases the phagocytic activity of macrophages and promotes phagosome maturation, allowing efficient capture and destruction of microbes (14).”
Background
Chronic Intestinal Inflammatory Condition Generates IL-10-Producing Regulatory B Cell Subset Characterized by CD1d Upregulation
Mizoguchi, A., Mizoguchi, E., Takedatsu, H., Blumberg, R. S., & Bhan, A. K. (2002) · Immunity · doi:10.1016/s1074-7613(02)00274-1 · Cited by 978 · cited 16× · see citing works
“IF N - γ (n g/ m l) MOG(35-55) (μg/ml) 0 20 30 40 10 0 20 40 50”
BackgroundMethodInfluential
Prevention of Arthritis by Interleukin 10–producing B Cells
Mauri, C., Gray, D., Mushtaq, N., & Londei, M. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021293 · Cited by 858 · cited 16× · see citing works
“IF N - γ (n g/ m l) MOG(35-55) (μg/ml) 0 20 30 40 10 0 20 40 50”
BackgroundMethodInfluential
Human Toll-Like Receptors Mediate Cellular Activation by Mycobacterium tuberculosis
Means, T. K., Wang, S., Lien, E., Yoshimura, A., Golenbock, D. T., & Fenton, M. J. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.7.3920 · Cited by 804 · cited 1× · see citing works
“Mammals possess at least 12 TLR that provide a powerful system to detect a broad range of pathogens including bacteria (2), mycobacteria (3), viruses (4), fungi (5), and helminths (6).”
Background
How can immunology contribute to the control of tuberculosis?
Kaufmann, S. H. E. (2001) · Nature reviews. Immunology · doi:10.1038/35095558 · Cited by 727 · see citing works
Plasmacytoid dendritic cells prime IL-10–producing T regulatory cells by inducible costimulator ligand
Ito, T., Yang, M., Wang, Y.-H., Lande, R., Gregorio, J. D., Perng, O. A., Qin, X.-F. F., Liu, Y.-J., & Gilliet, M. (2007) · Journal of Experimental Medicine · doi:10.1084/jem.20061660 · Cited by 686 · cited 16× · see citing works
“IF N - γ (n g/ m l) MOG(35-55) (μg/ml) 0 20 30 40 10 0 20 40 50”
BackgroundMethodInfluential
Distinct Effector Cytokine Profiles of Memory and Naive Human B Cell Subsets and Implication in Multiple Sclerosis
Duddy, M., Niino, M., Adatia, F., Hebert, S., Freedman, M., Atkins, H., Kim, H., & Bar-Or, A. (2007) · Journal of Immunology · doi:10.4049/jimmunol.178.10.6092 · Cited by 662 · cited 16× · see citing works
“IF N - γ (n g/ m l) MOG(35-55) (μg/ml) 0 20 30 40 10 0 20 40 50”
BackgroundMethodInfluential
Natural Recovery and Protection from Autoimmune Encephalomyelitis: Contribution of CD4+CD25+ Regulatory Cells within the Central Nervous System1
McGeachy, M., Stephens, L. A., & Anderton, S. (2005) · Journal of Immunology · doi:10.4049/jimmunol.175.5.3025 · Cited by 602 · cited 1× · see citing works
“B cells may also suppress pathogenic T cells by interacting with regulatory T cells (60), which are also necessary for disease resolution (61).”
BackgroundSelf-citation
TLR9 regulates Th1 responses and cooperates with TLR2 in mediating optimal resistance to Mycobacterium tuberculosis
Bafica, A., Scanga, C. A., Feng, C. G., Leifer, C., Cheever, A., & Sher, A. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20051782 · Cited by 601 · cited 1× · see citing works
“In agreement with that notion, although Mycobacterium tuberculosis can stimulate DC and macrophages to produce IL-12p40 via TLR-9 in vitro (65), we found that in B cells it induces IL-10 via TLR-2 and 4 but not TLR-9.”
Background
Novel Suppressive Function of Transitional 2 B Cells in Experimental Arthritis1
Evans, J., Chavez-Rueda, K., Eddaoudi, A., Meyer-Bahlburg, A., Rawlings, D., Ehrenstein, M., & Mauri, C. (2007) · Journal of Immunology · doi:10.4049/jimmunol.178.12.7868 · Cited by 591 · see citing works
Cutting Edge: MyD88 Is Required for Resistance to Toxoplasma gondii Infection and Regulates Parasite-Induced IL-12 Production by Dendritic Cells1
Scanga, C., Aliberti, J., Jankovic, D., Tilloy, F., Bennouna, S., Denkers, E., Medzhitov, R., & Sher, A. (2002) · Journal of Immunology · doi:10.4049/jimmunol.168.12.5997 · Cited by 547 · cited 1× · see citing works
“Mice lacking the TLR-signaling adaptor protein MyD88 show impaired survival upon infections with Staphylococcus aureus (8), Salmonella typhimurium (9), Toxoplasma gondii (10), or Mycobacterium tuberculosis (11), as a result of defects in both innate and adaptive immune defense mechanisms.”
Background
An Interleukin (IL)-10/IL-12 Immunoregulatory Circuit Controls Susceptibility to Autoimmune Disease
Segal, B., Dwyer, B. K., & Shevach, E. (1998) · Journal of Experimental Medicine · doi:10.1084/jem.187.4.537 · Cited by 534 · cited 1× · see citing works
“Such modulation of DC function could contribute to regulation of EAE because alteration of the IL-10/IL-12 cytokine balance has been shown to have important effects in this disease (56, 57).”
Background
B cells inhibit induction of T cell-dependent tumor immunity
Qin, Z.-H., Richter, G., Schüler, T., Ibe, S., Cao, X.-T., & Blankenstein, T. (1998) · Nature Medicine · doi:10.1038/nm0598-627 · Cited by 440 · cited 1× · see citing works
“Furthermore, B cells can limit antitumor immunity (70).”
Background
Faculty Opinions recommendation of Toll-like receptor engagement converts T-cell autoreactivity into overt autoimmune disease.
Conrad, D. (2005) · doi:10.3410/f.1021393.284813 · Cited by 439 · cited 1×
“As a consequence of their capacity to stimulate both innate and adaptive immunity, TLR agonists can be used to break immunological tolerance and induce autoimmune diseases such as arthritis (23), experimental autoimmune encephalomyelitis (EAE) (24), and diabetes (25).”
Background
Lipopolysaccharide-Activated B Cells Down-Regulate Th1 Immunity and Prevent Autoimmune Diabetes in Nonobese Diabetic Mice1
Tian, J.-D., Zekzer, D., Hanssen, L., Lu, Y., Olcott, A., & Kaufman, D. (2001) · Journal of Immunology · doi:10.4049/jimmunol.167.2.1081 · Cited by 421 · cited 1× · see citing works
“They also prevent autoimmune diabetes with a mechanism that possibly involves TGF- and FasL (59).”
Background
Distinct Profiles of Human B Cell Effector Cytokines: A Role in Immune Regulation?1
Duddy, M., Alter, A., & Bar-Or, A. (2004) · Journal of Immunology · doi:10.4049/jimmunol.172.6.3422 · Cited by 393 · cited 16× · see citing works
“IF N - γ (n g/ m l) MOG(35-55) (μg/ml) 0 20 30 40 10 0 20 40 50”
BackgroundMethodInfluential
Immunostimulatory DNA ameliorates experimental and spontaneous murine colitis
Rachmilewitz, D., Karmeli, F., Takabayashi, K., Hayashi, T., Leider–Trejo, L., Lee, J., Leoni, L. M., & Raz, E. (2002) · Gastroenterology · doi:10.1053/gast.2002.32994 · Cited by 380 · see citing works
Innate immunity mediated by TLR9 modulates pathogenicity in an animal model of multiple sclerosis
Prinz, M. (2006) · Journal of Clinical Investigation · doi:10.1172/jci26078 · Cited by 378 · cited 16× · see citing works
“IF N - γ (n g/ m l) MOG(35-55) (μg/ml) 0 20 30 40 10 0 20 40 50”
BackgroundMethodInfluential
Fatal Mycobacterium tuberculosis infection despite adaptive immune response in the absence of MyD88.
Fremond, C. M., Yeremeev, V., Nicolle, D., Jacobs, M., Quesniaux, V., & Ryffel, B. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200421027 · Cited by 357 · cited 1×
“Mice lacking the TLR-signaling adaptor protein MyD88 show impaired survival upon infections with Staphylococcus aureus (8), Salmonella typhimurium (9), Toxoplasma gondii (10), or Mycobacterium tuberculosis (11), as a result of defects in both innate and adaptive immune defense mechanisms.”
Background
Apoptotic cells protect mice from autoimmune inflammation by the induction of regulatory B cells
Gray, M., Miles, K., Salter, D. M., Gray, D., & Savill, J. (2007) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0700326104 · Cited by 340 · cited 1× · see citing works
“It is notable that other signals can also facilitate IL-10 production by B cells, such as apoptotic cells and some inflammatory mediators (62, 63).”
Background
Helminth Infection Protects Mice from Anaphylaxis via IL-10-Producing B Cells1
Mangan, N. E., Fallon, R., Smith, P., van Rooijen, N., McKenzie, A., & Fallon, P. (2004) · Journal of Immunology · doi:10.4049/jimmunol.173.10.6346 · Cited by 321 · cited 1× · see citing works
“For instance, the tropical helminth Schistosoma mansoni induces IL-10 production by B cells (78), and thereby protects mice from anaphylaxis (79).”
Background
B Cell Regulation of CD4+CD25+ T Regulatory Cells and IL-10 Via B7 is Essential for Recovery From Experimental Autoimmune Encephalomyelitis
Mann, M. K., Maresz, K., Shriver, L. P., Tan, Y., & Dittel, B. N. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.6.3447 · Cited by 316 · cited 1× · see citing works
“B cells may also suppress pathogenic T cells by interacting with regulatory T cells (60), which are also necessary for disease resolution (61).”
Background
Critical Roles of Myeloid Differentiation Factor 88-Dependent Proinflammatory Cytokine Release in Early Phase Clearance of Listeria monocytogenes in Mice1
Seki, E., Tsutsui, H., Tsuji, N., Hayashi, N., Adachi, K., Nakano, H., Futatsugi-Yumikura, S., Takeuchi, O., Hoshino, K., Akira, S., et al. (2002) · Journal of Immunology · doi:10.4049/jimmunol.169.7.3863 · Cited by 307 · cited 1× · see citing works
“Innate immune responses are severely impaired in mice lacking either TLR or MyD88, often leading to a fatal growth of infecting microbes (17, 18).”
Background
B Lymphocytes Regulate Dendritic Cell (Dc) Function in Vivo
Moulin, V., Andris, F., Thielemans, K., Maliszewski, C., Urbain, J., & Moser, M. (2000) · Journal of Experimental Medicine · doi:10.1084/jem.192.4.475 · Cited by 305 · cited 16× · see citing works
“IF N - γ (n g/ m l) MOG(35-55) (μg/ml) 0 20 30 40 10 0 20 40 50”
BackgroundMethodInfluential
Cytokines and adhesion molecules contribute to the ability of myelin proteolipid protein-specific T cell clones to mediate experimental allergic encephalomyelitis.
Kuchroo, V. K., Martin, C., Greer, J. M., Ju, S.-T., Sobel, R., & Dorf, M. (1993) · Journal of Immunology · doi:10.4049/jimmunol.151.8.4371 · Cited by 300 · cited 15× · see citing works
“IF N - γ (n g/ m l) MOG(35-55) (μg/ml) 0 20 30 40 10 0 20 40 50”
BackgroundMethodInfluential
Oligosaccharide-specific induction of interleukin 10 production by B220+ cells from schistosome-infected mice: a mechanism for regulation of CD4+ T-cell subsets
Velupillai, P., & Harn, D. A. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.1.18 · Cited by 299 · cited 1× · see citing works
“For instance, the tropical helminth Schistosoma mansoni induces IL-10 production by B cells (78), and thereby protects mice from anaphylaxis (79).”
Background
Intra-articularly localized bacterial DNA containing CpG motifs induces arthritis
Deng, G., Nilsson, I.-M., Verdrengh, M., Collins, L. V., & Tarkowski, A. (1999) · Nature Medicine · doi:10.1038/9554 · Cited by 295 · cited 1× · see citing works
“As a consequence of their capacity to stimulate both innate and adaptive immunity, TLR agonists can be used to break immunological tolerance and induce autoimmune diseases such as arthritis (23), experimental autoimmune encephalomyelitis (EAE) (24), and diabetes (25).”
Background
Cutting Edge: CpG Oligonucleotides Induce Splenic CD19+ Dendritic Cells to Acquire Potent Indoleamine 2,3-Dioxygenase-Dependent T Cell Regulatory Functions via IFN Type 1 Signaling
Mellor, A. L., Baban, B., Chandler, P., Manlapat, A., Kahler, D. J., & Munn, D. H. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.9.5601 · Cited by 285 · cited 16× · see citing works
“IF N - γ (n g/ m l) MOG(35-55) (μg/ml) 0 20 30 40 10 0 20 40 50”
BackgroundMethodInfluential
MyD88-Dependent but Toll-Like Receptor 2-Independent Innate Immunity to Listeria: No Role for Either in Macrophage Listericidal Activity1
Edelson, B., & Unanue, E. (2002) · Journal of Immunology · doi:10.4049/jimmunol.169.7.3869 · Cited by 274 · cited 1× · see citing works
“Innate immune responses are severely impaired in mice lacking either TLR or MyD88, often leading to a fatal growth of infecting microbes (17, 18).”
Background
The risk of relapses in multiple sclerosis during systemic infections
Correale, J. D., Fiol, M. P., & Gilmore, W. (2006) · Neurology · doi:10.1212/01.wnl.0000233834.09743.3b · Cited by 273 · cited 1× · see citing works
“Although it is known that infections can increase risk of exacerbation in relapsing-remitting MS (71), the mechanisms determining remissions are largely unknown.”
Background
Isatoribine, an agonist of TLR7, reduces plasma virus concentration in chronic hepatitis C infection
Horsmans, Y., Berg, T., Desager, J., Mueller, T., Schott, E., Fletcher, S., Steffy, K. R., Bauman, L., Kerr, B., & Averett, D. (2005) · Hepatology · doi:10.1002/hep.20839 · Cited by 249 · see citing works
Toll-Like Receptors Are Temporally Involved in Host Defense
Weiss, D. S., Raupach, B., Takeda, K., Akira, S., & Zychlinsky, A. (2004) · Journal of Immunology · doi:10.4049/jimmunol.172.7.4463 · Cited by 247 · cited 1× · see citing works
“Mice lacking the TLR-signaling adaptor protein MyD88 show impaired survival upon infections with Staphylococcus aureus (8), Salmonella typhimurium (9), Toxoplasma gondii (10), or Mycobacterium tuberculosis (11), as a result of defects in both innate and adaptive immune defense mechanisms.”
Background
B Cells Activated by Lipopolysaccharide, But Not By Anti-Ig and Anti-CD40 Antibody, Induce Anergy in CD8+ T Cells: Role of TGF-β11
Parekh, V., Prasad, D. V., Banerjee, P., Joshi, B., Kumar, A., & Mishra, G. C. (2003) · Journal of Immunology · doi:10.4049/jimmunol.170.12.5897 · Cited by 246 · cited 1× · see citing works
“For instance, TLR-activated B cells can directly anergize CD8 T cells via a cell-contact dependent mechanism involving TGF- 1 (58).”
Background
Toll-like receptor 9 signaling protects against murine lupus.
Wu, X.-B., & Peng, S. L. (2006) · Arthritis & Rheumatism · doi:10.1002/art.21553 · Cited by 246 · cited 1× · see citing works
“Deletion of tlr-9 worsens SLE in lupus-prone mice (33, 34), and polymorphisms in tlr-9 gene leading to lower TLR-9 expression can increase predisposition to SLE in human (35).”
Background
Recognition of fungal pathogens by Toll-like receptors
Netea, M., Graaf, C., Meer, J. T. M., & Kullberg, B. (2004) · European Journal of Clinical Microbiology and Infectious Diseases · doi:10.1007/s10096-004-1192-7 · Cited by 239 · cited 1× · see citing works
“Mammals possess at least 12 TLR that provide a powerful system to detect a broad range of pathogens including bacteria (2), mycobacteria (3), viruses (4), fungi (5), and helminths (6).”
Background
Viral recognition by Toll-like receptors
Barton, G. M. (2007) · Seminars in Immunology · doi:10.1016/j.smim.2007.01.003 · Cited by 209 · cited 1× · see citing works
“Mammals possess at least 12 TLR that provide a powerful system to detect a broad range of pathogens including bacteria (2), mycobacteria (3), viruses (4), fungi (5), and helminths (6).”
Background
How important are Toll‐like receptors for antimicrobial responses?
Carpenter, S., & O'Neill, L. A. J. (2007) · Cellular Microbiology · doi:10.1111/j.1462-5822.2007.00965.x · Cited by 182 · cited 1× · see citing works
“TLR play crucial roles in host defense mechanisms (7).”
Background
Vaccination with Empty Plasmid DNA or CpG Oligonucleotide Inhibits Diabetes in Nonobese Diabetic Mice: Modulation of Spontaneous 60-kDa Heat Shock Protein Autoimmunity1
Quintana, F., Rotem, A., Carmi, P., & Cohen, I. (2000) · Journal of Immunology · doi:10.4049/jimmunol.165.11.6148 · Cited by 170 · see citing works
Systemic application of CpG‐rich DNA suppresses adaptive T cell immunity via induction of IDO
Wingender, G., Garbi, N., Schumak, B., Jüngerkes, F., Endl, E., von Bubnoff, D., Steitz, J., Striegler, J., Moldenhauer, G., Tüting, T., et al. (2005) · European Journal of Immunology · doi:10.1002/eji.200535602 · Cited by 169 · cited 16× · see citing works
“IF N - γ (n g/ m l) MOG(35-55) (μg/ml) 0 20 30 40 10 0 20 40 50”
BackgroundMethodInfluential
Genetic variations of Toll-like receptor 9 predispose to systemic lupus erythematosus in Japanese population
Tao, K., Fujii, M., Tsukumo, S., Maekawa, Y., Kishihara, K., Kimoto, Y., Horiuchi, T., Hisaeda, H., Akira, S., Kagami, S., et al. (2007) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2006.065961 · Cited by 168 · cited 16× · see citing works
“IF N - γ (n g/ m l) MOG(35-55) (μg/ml) 0 20 30 40 10 0 20 40 50”
BackgroundMethodInfluential
CpG Oligonucleotides Are Potent Adjuvants for the Activation of Autoreactive Encephalitogenic T Cells In Vivo
Segal, B. M., Chang, J. T., & Shevach, E. M. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.11.5683 · Cited by 153 · cited 1× · see citing works
“As a consequence of their capacity to stimulate both innate and adaptive immunity, TLR agonists can be used to break immunological tolerance and induce autoimmune diseases such as arthritis (23), experimental autoimmune encephalomyelitis (EAE) (24), and diabetes (25).”
Background
New Generation Vaccine Induces Effective Melanoma-Specific CD8+ T Cells in the Circulation but Not in the Tumor Site
Appay, V., Jandus, C., Voelter, V., Reynard, S., Coupland, S. E., Rimoldi, D., Líénard, D., Guillaume, P., Krieg, A. Μ., Cerottini, J., et al. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.3.1670 · Cited by 150 · see citing works
IL-6 Increases Primed Cell Expansion and Survival
Rochman, I., Paul, W., & Ben-Sasson, S. (2005) · Journal of Immunology · doi:10.4049/jimmunol.174.8.4761 · Cited by 138 · cited 16× · see citing works
“IF N - γ (n g/ m l) MOG(35-55) (μg/ml) 0 20 30 40 10 0 20 40 50”
BackgroundMethodInfluential
Dendritic cell-derived IL-12 promotes B cell induction of Th2 differentiation: a feedback regulation of Th1 development.
Skok, J., Poudrier, J., & Gray, D. (1999) · Journal of Immunology · doi:10.4049/jimmunol.163.8.4284 · Cited by 125 · see citing works
T Cell Accumulation in B Cell Follicles Is Regulated by Dendritic Cells and Is Independent of B Cell Activation
Fillatreau, S., & Gray, D. (2003) · Journal of Experimental Medicine · doi:10.1084/jem.20021750 · Cited by 124 · cited 16× · see citing works
“IF N - γ (n g/ m l) MOG(35-55) (μg/ml) 0 20 30 40 10 0 20 40 50”
BackgroundMethodInfluentialSelf-citation
Protection against autoimmune nephritis in MyD88-deficient MRL/lpr mice.
Sadanaga, A., Nakashima, H., Akahoshi, M., Masutani, K., Miyake, K., Igawa, T., Sugiyama, N., Niiro, H., & Harada, M. (2007) · Arthritis & Rheumatism · doi:10.1002/art.22571 · Cited by 118 · cited 1×
“The contribution of TLR signaling to autoimmune diseases is also indicated by the requirement for MyD88 in spontaneous development of systemic lupus erythematosus (SLE) in lupus-prone mice (26, 27).”
Background
Effect of anti-tumor necrosis factor alpha antibodies on histopathology of primary Salmonella infections
Mastroeni, P., Skepper, J., & Hormaeche, C. (1995) · Infection and Immunity · doi:10.1128/iai.63.9.3674-3682.1995 · Cited by 118 · cited 1× · see citing works
“Furthermore, TLR-activated macrophages secrete inflammatory cytokines driving formation of granuloma (15), which limits dissemination of the microbe, and also produce effector substances directly associated with microbe killing (16).”
Background
Evaluation of surgery for Parkinson's disease: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.
Montgomery, E. (2000) · Neurology · doi:10.1212/wnl.55.1.154 · Cited by 112 · cited 1×
“Furthermore, a Mycobacterium bovis strain bacillus Calmette-Guérin vaccine has been used to treat MS patients, and resulted in a significant reduction in lesions measured by gadolinium-enhanced magnetic resonance imaging (74).”
Method
Modulation of renal disease in autoimmune NZB/NZW mice by immunization with bacterial DNA.
Gilkeson, G. S., Ruiz, P., Pippen, A. M., Alexander, A. L., Lefkowith, J. B., & Pisetsky, D. S. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.4.1389 · Cited by 109 · see citing works
Schistosome larvae stimulate macrophage cytokine production through TLR4-dependent and -independent pathways
Jenkins, S., Hewitson, J. P., Ferret-Bernard, S., & Mountford, A. (2005) · International Immunology · doi:10.1093/intimm/dxh319 · Cited by 91 · cited 1× · see citing works
“Mammals possess at least 12 TLR that provide a powerful system to detect a broad range of pathogens including bacteria (2), mycobacteria (3), viruses (4), fungi (5), and helminths (6).”
Background
Inflammatory arthritis can be reined in by CpG-induced DC–NK cell cross talk
Wu, H.-J. J., Sawaya, H., Binstadt, B. A., Brickelmaier, M., Blasius, A. L., Gorelik, L., Mahmood, U., Weissleder, R., Carulli, J. P., Benoist, C. O., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070285 · Cited by 90 · cited 1× · see citing works
“CD8 DC can protect mice from arthritis after CpG administration (29).”
Background
High IL-13 production by human neonatal T cells: neonate immune system regulator?
Ribeiro-do-Couto, L. M., Boeije, L. C. M., Kroon, J., Hooibrink, B., Breur-Vriesendorp, B. S., Aarden, L. A., & Boog, C. J. P. (2001) · European Journal of Immunology · doi:10.1002/1521-4141(200111)31:11 · Cited by 80 · see citing works
A Role for Inflammatory Mediators in the Induction of Immunoregulatory B Cells1
Matsumura, Y., Byrne, S., Nghiem, D., Miyahara, Y., & Ullrich, S. (2006) · Journal of Immunology · doi:10.4049/jimmunol.177.7.4810 · Cited by 79 · cited 1× · see citing works
“It is notable that other signals can also facilitate IL-10 production by B cells, such as apoptotic cells and some inflammatory mediators (62, 63).”
Background
Modulation of the IL-10/IL-12 cytokine circuit by interferon-β inhibits the development of epitope spreading and disease progression in murine autoimmune encephalomyelitis
Tuohy, V. K., Yu, M., Yin, L., Mathisen, P. M., Johnson, J. M., & Kawczak, J. A. (2000) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(00)00384-2 · Cited by 74 · cited 1× · see citing works
“Such modulation of DC function could contribute to regulation of EAE because alteration of the IL-10/IL-12 cytokine balance has been shown to have important effects in this disease (56, 57).”
Background
MyD88‐dependent autoimmune disease in Lyn‐deficient mice
Silver, K. L., Crockford, T., Bouriez‐Jones, T., Milling, S., Lambe, T., & Cornall, R. (2007) · European Journal of Immunology · doi:10.1002/eji.200737293 · Cited by 71 · cited 1× · see citing works
“The contribution of TLR signaling to autoimmune diseases is also indicated by the requirement for MyD88 in spontaneous development of systemic lupus erythematosus (SLE) in lupus-prone mice (26, 27).”
Background
Infection with Mycobacterium bovis BCG Diverts Traffic of Myelin Oligodendroglial Glycoprotein Autoantigen-Specific T Cells Away from the Central Nervous System and Ameliorates Experimental Autoimmune Encephalomyelitis
Sewell, D. L., Reinke, E., Co, D. O., Hogan, L. H., Fritz, R., Sandor, M., & Fabry, Z. (2003) · Clinical Diagnostic Laboratory Immunology · doi:10.1128/cdli.10.4.564-572.2003 · Cited by 66 · cited 3×
“As further support of that notion, EAE can be prevented by prior injection of killed Tubercle bacillus (75, 76) or infection with bacillus Calmette-Guérin (77).”
Background
Bacterial agents protect against autoimmune disease. I. Mice pre-exposed to Bordetella pertussis or Mycobacterium tuberculosis are highly refractory to induction of experimental autoimmune encephalomyelitis.
Lehmann, D., & ben-Nun, A. (1992) · Journal of Autoimmunity · doi:10.1016/0896-8411(92)90185-s · Cited by 63 · cited 1×
“As further support of that notion, EAE can be prevented by prior injection of killed Tubercle bacillus (75, 76) or infection with bacillus Calmette-Guérin (77).”
Background
Risk factors in multiple sclerosis: Tuberculin reactivity, age at measles infection, tonsillectomy and appendectomy
Andersen, E., Isager, H., & Hyllested, K. (1981) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.1981.tb00756.x · Cited by 52 · cited 1× · see citing works
“An inverse correlation between previous exposure to Mycobacterium tuberculosis and MS incidence has been observed, suggesting that mycobacteria infections can protect from MS (73).”
Background
Prevention of Allergic Encephalomyelitis by Prior Injection of Adjuvants
Kies, M., & Alvord, E. (1958) · Nature · doi:10.1038/1821106a0 · Cited by 52 · cited 1×
“As further support of that notion, EAE can be prevented by prior injection of killed Tubercle bacillus (75, 76) or infection with bacillus Calmette-Guérin (77).”
Background
Lipopolysaccharide pretreatment modulates the disease course in experimental autoimmune encephalomyelitis.
Buenafe, A., & Bourdette, D. (2007) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.09.004 · Cited by 48 · see citing works

Flagged first, then by citations

2 of the 81 references couldn’t be matched to a known paper.

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Inflammation and tumor progression: signaling pathways and targeted intervention
Zhao, H., Wu, L., Yan, G., Chen, Y., Zhou, M., Wu, Y., & Li, Y. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00658-5 · Cited by 2,907 · see citing works
Immune regulatory function of B cells.
Mauri, C., & Bosma, A. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-074934 · Cited by 1,278 · see citing works
Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination
Berer, K., Mues, M., Koutrolos, M., Rasbi, Z. A., Boziki, M., Johner, C., Wekerle, H., & Krishnamoorthy, G. (2011) · Nature · doi:10.1038/nature10554 · Cited by 1,251 · see citing works
IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases
Shen, P., Roch, T., Lampropoulou, V., O’Connor, R. A., Stervbo, U., Hilgenberg, E., Ries, S., Dang, V. D., Jaimes, Y., Daridon, C., et al. (2014) · Nature · doi:10.1038/nature12979 · Cited by 1,048 · see citing works
Self-citation
B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6–producing B cells
Barr, T., Shen, P., Brown, S., Lampropoulou, V., Roch, T., Lawrie, S., Fan, B.-L., O'Connor, R., Anderton, S., Bar-Or, A., et al. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20111675 · Cited by 650 · see citing works
“However, the production of IL-10 in mice (Lampropoulou et al., 2008; Barr et al., 2010; Neves et al., 2010) and humans (Bouaziz et al., 2010) is strongly augmented by TLR signals and, indeed, these innate signals are required in vivo for the full expression of regulatory activity (Lampropoulou et…”
BackgroundMethodResultInfluentialSelf-citation
Microbiota-Derived Metabolites Suppress Arthritis by Amplifying Aryl-Hydrocarbon Receptor Activation in Regulatory B Cells
Rosser, E. C., Piper, C. J. M., Matei, D. E., Blair, P. A., Rendeiro, A. F., Orford, M., Alber, D. G., Krausgruber, T., Catalan, D., Klein, N., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.03.003 · Cited by 579 · see citing works
“Published by Elsevier Inc. 1 er the CC BY license (http://creativecommons.org/licenses/by/4.0/). levels of inflammatory cytokines, for example IFNa and/or IL-1b and IL-6, induce IL-10-producing Breg differentiation (Lampropoulou et al., 2008; Menon et al., 2016; Rosser et al., 2014).”
BackgroundInfluential
Interleukin-10-producing plasmablasts exert regulatory function in autoimmune inflammation.
Matsumoto, M., Baba, A., Yokota, T., Nishikawa, H., Ohkawa, Y., Kayama, H., Kallies, A., Nutt, S., Sakaguchi, S., Takeda, K., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.10.016 · Cited by 543 · see citing works
Abnormal B‐cell cytokine responses a trigger of T‐cell–mediated disease in MS?
Bar-Or, A., Fawaz, L. M., Fan, B.-L., Darlington, P., Rieger, A., Ghorayeb, C., Calabresi, P., Waubant, E., Hauser, S. L., Zhang, J., et al. (2010) · Annals of Neurology · doi:10.1002/ana.21939 · Cited by 521 · see citing works
“In recent years, the ‘2-signal’ model of normal human B-cell activation (involving BCR and CD40 engagement) has been extended to include ‘3rd signals’ that can modulate B-cell responses.(18,21,25,27,32) In relation to B-cell effector cytokine production, we previously reported that upon standard 2-signal activation, B…”
Background
Antibody-independent functions of B cells: a focus on cytokines
Shen, P., & Fillatreau, S. (2015) · Nature Reviews Immunology · doi:10.1038/nri3857 · Cited by 508 · see citing works
Self-citation
The Development and Function of Regulatory B Cells Expressing IL-10 (B10 Cells) Requires Antigen Receptor Diversity and TLR Signals
Yanaba, K., Bouaziz, J.-D., Matsushita, T., Tsubata, T., & Tedder, T. F. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0900270 · Cited by 503 · see citing works
“SJL mice are susceptible to EAE after myelin proteolipid protein immunization (38).”
BackgroundInfluential
B10 cells and regulatory B cells balance immune responses during inflammation, autoimmunity, and cancer
DiLillo, D. J., Matsushita, T., & Tedder, T. F. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.05137.x · Cited by 430 · see citing works
Regulatory B Cells (B10 Cells) and Regulatory T Cells Have Independent Roles in Controlling Experimental Autoimmune Encephalomyelitis Initiation and Late-Phase Immunopathogenesis
Matsushita, T., Horikawa, M., Iwata, Y., & Tedder, T. F. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001307 · Cited by 394 · see citing works
“(44) have also shown that tissue culture supernatant fluid from LPS-stimulated spleen”
IL-10: A Multifunctional Cytokine in Viral Infections
Rojas, J. M., Avia, M., Martı́n, V., & Sevilla, N. (2017) · Journal of Immunology Research · doi:10.1155/2017/6104054 · Cited by 414 · see citing works
Reassessing B cell contributions in multiple sclerosis
Li, R., Patterson, K. R., & Bar‐Or, A. (2018) · Nature Immunology · doi:10.1038/s41590-018-0135-x · Cited by 397 · see citing works
Immunosuppressive Mechanisms of Regulatory B Cells
Catalán, D., Mansilla, M. A., Ferrier, A., Soto, L., Oļeiņika, K., Aguillón, J. C., & Aravena, O. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.611795 · Cited by 407 · see citing works
“This evidence, together with data showing that IL-10 B cells or plasmablasts inhibit Th1 and Th17-inducing DCs or induce tolerogenic DCs, in addition to direct inhibition of Th1 and Th17 cells, contribute to clarify the suppressive role of B10 in EAE and other inflammatory conditions (55, 92, 306, 307).”
BackgroundResult
Integration of B cell responses through Toll-like receptors and antigen receptors
Rawlings, D. J., Schwartz, M. A., Jackson, S. W., & Meyer‐Bahlburg, A. (2012) · Nature reviews. Immunology · doi:10.1038/nri3190 · Cited by 337 · see citing works
Role of B cells as antigen presenting cells
Rastogi, I., Jeon, D., Moseman, J. E., Muralidhar, A., Potluri, H. K., & McNeel, D. G. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.954936 · Cited by 352 · see citing works
“Several B cell subsets, such as immature B cells, plasmablasts and mature B cells, have been shown to differentiate into IL-10-producing Bregs, upon stimulation with toll-like receptors (TLRs) and/or CD40 activation (93, 94).”
Background
IL-10 producing regulatory B cells in the pathogenesis of chronic HBV infection
Das, A., Ellis, G., Pallant, C., Lopes, A., Khanna, P., Peppa, D., Chen, A., Blair, P., Dusheiko, G., Gill, U., et al. (2012) · Journal of Immunology · doi:10.4049/jimmunol.1103139 · Cited by 333 · see citing works
“PBMCs were stimulated with CpG, a TLR-9 agonist, relevant in the context of the DNA virus HBV, which was shown to potently induce B cell IL-10 release (14, 24, 25).”
Method
Not always the bad guys: B cells as regulators of autoimmune pathology
Fillatreau, S., Gray, D., & Anderton, S. (2008) · Nature reviews. Immunology · doi:10.1038/nri2315 · Cited by 323 · see citing works
Self-citation
Toll-like receptors (TLRs) and Nod-like receptors (NLRs) in inflammatory disorders
Fukata, M., Vamadevan, A. S., & Abreu, M. T. (2009) · Seminars in Immunology · doi:10.1016/j.smim.2009.06.005 · Cited by 317 · see citing works
Mechanisms of immune regulation in allergic diseases: the role of regulatory T and B cells
Palomares, Ó., Akdis, M., Martín‐Fontecha, M., & Akdiş, C. A. (2017) · Immunological Reviews · doi:10.1111/imr.12555 · Cited by 336 · see citing works
BCG-Induced Cross-Protection and Development of Trained Immunity: Implication for Vaccine Design
Covián, C., Fernández‐Fierro, A., Retamal-Díaz, A. R., Díaz, F. E., Vasquez, A. E., Lay, M. K., Riedel, C. A., González, P. A., Bueno, S. M., & Kalergis, A. M. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02806 · Cited by 329 · see citing works
“Also, TLR-signaling stimulated by mycobacterial components induces IL-10 secretion by B cells and consequent suppression of Th1 and Th17 activities, contributing to the suppression of autoimmune reactions (90).”
Background
Signaling via the MyD88 Adaptor Protein in B Cells Suppresses Protective Immunity during Salmonella typhimurium Infection
Neves, P., Lampropoulou, V., Calderón‐Gómez, E., Roch, T., Stervbo, U., Shen, P., Kühl, A. A., Loddenkemper, C., Haury, M., Nedospasov, S. A., et al. (2010) · Immunity · doi:10.1016/j.immuni.2010.10.016 · Cited by 307 · see citing works
“Alternatively, the recently identified role of MyD88 in the suppressive functions of B cells in EAE (Lampropoulou et al., 2008) suggests that ablation ofMyd88 specifically in B cells could unleash cell-mediated immune responses and improve protection against pathogens.”
InfluentialSelf-citation
Human CD19(+)CD25(high) B regulatory cells suppress proliferation of CD4(+) T cells and enhance Foxp3 and CTLA-4 expression in T-regulatory cells.
Kessel, A., Haj, T., Peri, R., Snir, A., Melamed, D., Sabo, E., & Toubi, E. (2012) · Autoimmunity Reviews · doi:10.1016/j.autrev.2011.11.018 · Cited by 291 · see citing works
“B cell expression of B7 (CD86) co-stimulatory molecule was proven to be necessary for B-cell mediated suppression of EAE [33].”
Influential
Transgenic Inhibition of Astroglial NF-κB Improves Functional Outcome in Experimental Autoimmune Encephalomyelitis by Suppressing Chronic Central Nervous System Inflammation
Brambilla, R., Persaud, T., Hu, X.-C., Karmally, S., Shestopalov, V., Dvoriantchikova, G., Ivanov, D., Nathanson, L., Barnum, S., & Bethea, J. (2009) · Journal of Immunology · doi:10.4049/jimmunol.0802954 · Cited by 285 · see citing works
“Specifically, IL-10-producing B cells stimulate resolution of EAE (37), and this appears to be linked to TLR activation (38).”
Background
Toll-like receptor signalling in B cells during systemic lupus erythematosus
Fillatreau, S., Manfroi, B., & Dörner, T. (2020) · Nature Reviews Rheumatology · doi:10.1038/s41584-020-00544-4 · Cited by 280
Self-citation
A Novel IL-10-Independent Regulatory Role for B Cells in Suppressing Autoimmunity by Maintenance of Regulatory T Cells via GITRL
Ray, A., Basu, S., Williams, C. B., Salzman, N., & Dittel, B. (2012) · Journal of Immunology · doi:10.4049/jimmunol.1103354 · Cited by 278 · see citing works
“In regard to TLR ligands, the TLR-signaling adaptor protein MyD88 was found to be essential for induction of EAE when globally knocked out, but not when deficient in B cells (52).”
Background
B cells as therapeutic targets in SLE
Sanz, I., & Lee, F. E. (2010) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2010.68 · Cited by 275 · see citing works
The Calcium Sensors STIM1 and STIM2 Control B Cell Regulatory Function through Interleukin-10 Production
Matsumoto, M., Fujii, Y., Baba, A., Hikida, M., Kurosaki, T., & Baba, Y. (2011) · Immunity · doi:10.1016/j.immuni.2011.03.016 · Cited by 262 · see citing works
IL‐10 produced by activated human B cells regulates CD4+ T‐cell activation in vitro
Bouaziz, J., Calbo, S., Maho-Vaillant, M., Saussine, A., Bagot, M., Bensussan, A., & Musette, P. (2010) · European Journal of Immunology · doi:10.1002/eji.201040673 · Cited by 261 · see citing works
Toll‐like receptors – sentries in the B‐cell response
Bekeredjian-Ding, I., & Jego, G. (2009) · Immunology · doi:10.1111/j.1365-2567.2009.03173.x · Cited by 249 · see citing works
Role of regulatory B cells in immune tolerance to allergens and beyond.
van de Veen, W., Stanić, B., Wirz, O., Jansen, K., Głobińska, A., & Akdiş, M. (2016) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2016.07.006 · Cited by 239 · see citing works
The Regulatory Role of IL-10 in Neurodegenerative Diseases
Porro, C., Cianciulli, A., & Panaro, M. (2020) · Biomolecules · doi:10.3390/biom10071017 · Cited by 235 · see citing works
“Consistent to this finding, previous studies reported that CD40 stimulation triggered continuous IL-10 production by human B cells in response to TLR stimulation correlating with B cell-mediated recovery from EAE by IL-10 production [48,49], promising a novel therapeutic approach for MS.”
Result
Regulatory B cells in autoimmune diseases
Yang, M., Rui, K., Wang, S.-J., & Lu, L.-W. (2013) · Cellular & Molecular Immunology · doi:10.1038/cmi.2012.60 · Cited by 213 · see citing works
Regulation of Toll-Like Receptor (TLR) Signaling Pathway by Polyphenols in the Treatment of Age-Linked Neurodegenerative Diseases: Focus on TLR4 Signaling
Azam, S., Jakaria, M., Kim, I.-S., Kim, J., Haque, M. E., & Choi, D. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01000 · Cited by 207 · see citing works
The Conserved Scavenger Receptor Cysteine-Rich Superfamily in Therapy and Diagnosis
Martínez, V. G., Moestrup, S. K., Holmskov, U., Mollenhauer, J., & Lozano, F. (2011) · Pharmacological Reviews · doi:10.1124/pr.111.004523 · Cited by 187 · see citing works
“…in the presence of microbial ligands of these PRRs has important consequences for the expansion and function of different T and B cell types, with effector as well as regulatory function (Netea et al., 2004; Caron et al., 2005; Liu et al., 2006; Lampropoulou et al., 2008; Yanaba et al., 2009).”
BackgroundResult
Modeling the heterogeneity of multiple sclerosis in animals
Simmons, S. B., Pierson, E. R., Lee, S. Y., & Goverman, J. M. (2013) · Trends in Immunology · doi:10.1016/j.it.2013.04.006 · Cited by 176 · see citing works
Periductal interleukin‐17 production in association with biliary innate immunity contributes to the pathogenesis of cholangiopathy in primary biliary cirrhosis
Harada, K., Shimoda, S., Sato, Y., Isse, K., Ikeda, H., & Nakanuma, Y. (2009) · Clinical and Experimental Immunology · doi:10.1111/j.1365-2249.2009.03947.x · Cited by 183 · see citing works
Regulatory B cells in autoimmunity: developments and controversies
Mauri, C., & Blair, P. (2010) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2010.140 · Cited by 181 · see citing works
Regulatory B cells in cancer
Michaud, D., Steward, C. R., Mirlekar, B., & Pylayeva-Gupta, Y. (2020) · Immunological Reviews · doi:10.1111/imr.12939 · Cited by 179 · see citing works
Aryl Hydrocarbon Receptor Contributes to the Transcriptional Program of IL-10-Producing Regulatory B Cells
Piper, C. J. M., Rosser, E., Oļeiņika, K., Nistala, K., Krausgruber, T., Rendeiro, A. F., Banos, A., Drozdov, I., Villa, M., Thomson, S., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.10.018 · Cited by 168 · see citing works
“B cell receptor (BCR) engagement, Toll-like receptor (TLR) agonists lipopolysaccharide (LPS; TLR2 and TLR4) (Lampropoulou et al., 2008; Tian et al., 2001), CpG oligo-deoxynucleotides (TLR9), and inflammatory cytokines such as IL-1b and IL-6 or IFN-a are all potent inducers of B cell-derived IL-10, suggesting an import…”
Background
Regulatory B Cells Shape the Development of Th2 Immune Responses in BALB/c Mice Infected with Leishmania major Through IL-10 Production
Ronet, C., Torre, Y. H.-L., Revaz-Breton, M., Mastelic, B., Tacchini-Cottier, F., Louis, J., & Launois, P. (2009) · Journal of Immunology · doi:10.4049/jimmunol.0901114 · Cited by 166 · see citing works
“Furthermore, in the EAE model, recovery was associated with the suppression of IL-12 production by DCs by IL-10 secreted by B cells (8, 45).”
Background
The immune potential and immunopathology of cytokine-producing B cell subsets: a comprehensive review.
Bao, Y., & Cao, X.-T. (2014) · Journal of Autoimmunity · doi:10.1016/j.jaut.2014.04.001 · Cited by 161 · see citing works
Human T cells induce their own regulation through activation of B cells.
Lemoine, S., Morva, A., Youinou, P., & Jamin, C. (2011) · Journal of Autoimmunity · doi:10.1016/j.jaut.2011.01.005 · Cited by 159
Toll-like receptors regulate B cell cytokine production in patients with diabetes
Jagannathan, M., McDonnell, M., Liang, Y., Hasturk, H., Hetzel, J., Rubin, D., Kantarci, A., Van Dyke, T. E., Ganley-Leal, L. M., & Nikolajczyk, B. S. (2010) · Diabetologia · doi:10.1007/s00125-010-1730-z · Cited by 156 · see citing works
“TLR engagement can activate B cell IL-10 production, which is critical for inflammatory disease resolution [26].”
Background
Tolerant Kidney Transplant Patients Produce B Cells with Regulatory Properties.
Chesneau, M., Michel, L., Dugast, E., Chenouard, A., Baron, D., Pallier, A., Durand, J., Braza, F., Guerif, P., Laplaud, D., et al. (2015) · Journal of the American Society of Nephrology · doi:10.1681/asn.2014040404 · Cited by 156 · see citing works
Evaluating the role of Toll-like receptors in diseases of the central nervous system.
Carty, M., & Bowie, A. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.01.003 · Cited by 154 · see citing works
“from B cells which prevents the release of IL-6 from DCs [57].”
Background
MHC class II–restricted antigen presentation by plasmacytoid dendritic cells inhibits T cell–mediated autoimmunity
Irla, M., Küpfer, N., Suter, T. B., Lissilaa, R., Benkhoucha, M., Skupsky, J., Lalive, P. H., Fontana, A., Reith, W., & Hugues, S. (2010) · The Journal of Experimental Medicine · doi:10.1084/jem.20092627 · Cited by 139 · see citing works
“In accordance with previous studies (Fillatreau et al., 2002; Lampropoulou et al., 2008; by promoting the selective expansion of natural T reg cells.”
ResultInfluential
Regulation of B‐cell responses by Toll‐like receptors
Browne, E. (2012) · Immunology · doi:10.1111/j.1365-2567.2012.03587.x · Cited by 150 · see citing works
TLR-2–Activated B Cells Suppress Helicobacter-Induced Preneoplastic Gastric Immunopathology by Inducing T Regulatory-1 Cells
Sayi, A., Kohler, E., Toller, I., Flavell, R., Müller, W., Roers, A., & Müller, A. (2011) · Journal of Immunology · doi:10.4049/jimmunol.1002269 · Cited by 146 · see citing works
“All B cells can, in principle, produce IL-10 upon TLR-2, -4, or -9 stimulation or T cell-dependent activation (14, 15), with particularly strong production being attributed to CD5 peritoneal B-1a cells (16), intestinal CD19CD1d cells (9), and splenic CD1dCD5 “B10” cells (8).”
Background
Unique B Cell Differentiation Profile in Tolerant Kidney Transplant Patients
Chesneau, M., Pallier, A., Braza, F., Lacombe, G., Gallou, S. L., Baron, D., Giral, M., Danger, R., Guerif, P., Aubert-Wastiaux, H., et al. (2014) · American Journal of Transplantation · doi:10.1111/ajt.12508 · Cited by 144 · see citing works
Induction of a regulatory B cell population in experimental allergic encephalomyelitis by alteration of the gut commensal microflora
Ochoa-Repáraz, J., Mielcarz, D., Haque-Begum, S., & Kasper, L. (2010) · Gut microbes · doi:10.4161/gmic.1.2.11515 · Cited by 142 · see citing works
Regulatory functions of innate-like B cells
Zhang, X. (2013) · Cellular & Molecular Immunology · doi:10.1038/cmi.2012.63 · Cited by 140 · see citing works
Regulation of immunity and autoimmunity by B cells.
Mauri, C. (2010) · Current Opinion in Immunology · doi:10.1016/j.coi.2010.10.009 · Cited by 137 · see citing works
“These mice develop exacerbated EAE compared to wild-type mice [37].”
Background
Regulation of Interleukin-10 Expression
Rutz, S., & Ouyang, W. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-94-024-0921-5_5 · Cited by 166 · see citing works
B cells and Autoimmunity
Pillai, S., Mattoo, H., & Cariappa, A. (2011) · Current Opinion in Immunology · doi:10.1016/j.coi.2011.10.007 · Cited by 132 · see citing works
“Since lupus pathogenesis is driven by chromatin derived autoantigens that can both engage the BCR and activate endosomal TLRs, auto-antigen specific B cell differentiation into long-lived plasma cells may occur more readily in this disease than in many other auto-immune disorders.”
BackgroundInfluential
Toll‐like Receptors in Autoimmunity
Fischer, M., & Ehlers, M. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1443.012 · Cited by 132 · see citing works
The Dynamics of B Cell Aging in Health and Disease
de Mol, J., Kuiper, J., Tsiantoulas, D., & Foks, A. C. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.733566 · Cited by 155 · see citing works
“In the adaptive pathway, BREGS present antigens to CD4 T cells and become activated through CD40-CD40L and IL-21 signals (77), whereas in the innate pathway, TLR2 and TLR9 signaling and IL-1b play important roles (78).”
Background
BAFF inhibition attenuates fibrosis in scleroderma by modulating the regulatory and effector B cell balance
Matsushita, T., Kobayashi, T., Mizumaki, K., Kano, M., Sawada, T., Tennichi, M., Okamura, A., Hamaguchi, Y., Iwakura, Y., Hasegawa, M., et al. (2018) · Science Advances · doi:10.1126/sciadv.aas9944 · Cited by 131 · see citing works
“The CD40-CD40L interaction and antigen-specific signals were reported to be essential for IL-10 production from B cells (3), while TLR signals strongly augment the production of IL-10 in mice (23) and humans (24).”
Background
Suppressive functions of activated B cells in autoimmune diseases reveal the dual roles of Toll‐like receptors in immunity
Lampropoulou, V., Calderon‐Gomez, E., Roch, T., Neves, P., Shen, P., Stervbo, U., Boudinot, P., Anderton, S. M., & Fillatreau, S. (2010) · Immunological Reviews · doi:10.1111/j.0105-2896.2009.00855.x · Cited by 130 · see citing works
“Naive B cells must first receive a specific signal before they can produce IL10 upon BCR ⁄CD40 stimulation.”
BackgroundInfluentialSelf-citation
Autocrine IL‐10 promotes human B‐cell differentiation into IgM‐ or IgG‐secreting plasmablasts
Heine, G., Drozdenko, G., Grün, J. R., Chang, H.-D., Radbruch, A., & Worm, M. (2014) · European Journal of Immunology · doi:10.1002/eji.201343822 · Cited by 127 · see citing works
TLR‐mediated STAT3 and ERK activation controls IL‐10 secretion by human B cells
Liu, B.-S., Cao, Y., Huizinga, T., Hafler, D., & Toes, R. (2014) · European Journal of Immunology · doi:10.1002/eji.201344341 · Cited by 123 · see citing works
Regulatory B cells in ANCA-associated vasculitis
Wilde, B., Thewissen, M., Damoiseaux, J., Knippenberg, S., Hilhorst, M., van Paassen, P., Witzke, O., & Tervaert, J. C. (2013) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2012-202986 · Cited by 122 · see citing works
NFATc1 affects mouse splenic B cell function by controlling the calcineurin–NFAT signaling network
Bhattacharyya, S., Deb, J., Patra, A., Pham, D. A. T., Chen, W., Vaeth, M., Berberich-Siebelt, F., Klein-Hessling, S., Lamperti, E., Reifenberg, K., et al. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20100945 · Cited by 122 · see citing works
“This suppressive effect of NFATc1/ B cells was markedly reduced by adding the IL-10–specific antibody JES5-2A5, which relieved IL-10–mediated inhibition of cytokine production of T cells by B cells (Lampropoulou et al., 2008).”
BackgroundMethodInfluential
From the regulatory functions of B cells to the identification of cytokine-producing plasma cell subsets
Dang, V. D., Hilgenberg, E., Ries, S., Shen, P., & Fillatreau, S. (2014) · Current Opinion in Immunology · doi:10.1016/j.coi.2014.02.009 · Cited by 125 · see citing works
Self-citation
Effector and regulatory B cells in immune-mediated kidney disease
Oļeiņika, K., Mauri, C., & Salama, A. (2018) · Nature Reviews Nephrology · doi:10.1038/s41581-018-0074-7 · Cited by 115 · see citing works
Killer B lymphocytes: the evidence and the potential
Lundy, S. K. (2009) · Inflammation Research · doi:10.1007/s00011-009-0014-x · Cited by 113 · see citing works
An age-related numerical and functional deficit in CD19+CD24hiCD38hi B cells is associated with an increase in systemic autoimmunity
Duggal, N. A., Upton, J., Phillips, A. C., Sapey, E., & Lord, J. (2013) · Aging Cell · doi:10.1111/acel.12114 · Cited by 110 · see citing works
“Expression of TLR1, TLR2, TLR4, TLR7 and TLR9 transcripts has been reported on B cells (Barr et al., 2007), and TLR-activated B cells are capable of resolving autoimmune disorders by inhibiting pathogenic T cells via IL10 production (Lampropoulou et al., 2008).”
Background
Cytokine-Defined B Cell Responses as Therapeutic Targets in Multiple Sclerosis
Li, R., Rezk, A., Healy, L. M., Muirhead, G., Prat, A., Gommerman, J. L., & Bar‐Or, A. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00626 · Cited by 100 · see citing works
“For example, innate signal-induced IL-10-producing B cells are able to down-regulate pathogenic T-cell responses indirectly through dendritic cells (14), whereas adaptive signal-induced IL-10-producing B cells directly down-regulate antigen-specific T-cell responses (15, 16).”
Background
Transcriptomics identify CD9 as a marker of murine IL10-competent regulatory B cells
Sun, J.-B., Wang, J.-G., Pefanis, E., Chao, J. L., Rothschild, G., Tachibana, I., Chen, J.-K., Ivanov, I., Rabadán, R., Takeda, Y., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.09.070 · Cited by 107 · see citing works
“Bregs are found enriched in phenotypically diverse B-cell subsets.”
BackgroundInfluential
B cells from glatiramer acetate-treated mice suppress experimental autoimmune encephalomyelitis
Kala, M., Rhodes, S. N., Piao, W.-H., Shi, F., Campagnolo, D. I., & Vollmer, T. L. (2009) · Experimental Neurology · doi:10.1016/j.expneurol.2009.10.015 · Cited by 103 · see citing works
Regulatory B cells: the cutting edge of immune tolerance in kidney transplantation
Peng, B., Ming, Y., & Yang, C. (2018) · Cell Death and Disease · doi:10.1038/s41419-017-0152-y · Cited by 103 · see citing works
Helminth Antigens Modulate Immune Responses in Cells from Multiple Sclerosis Patients through TLR2-Dependent Mechanisms
Correale, J. D., & Farez, M. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0900897 · Cited by 100 · see citing works
“TLR9 contributes to EAE severity (52) but has no influence on B cell-driven disease resolution (51).”
BackgroundInfluential
Cellular targets of regulatory B cell-mediated suppression.
Rosser, E., Blair, P., & Mauri, C. (2014) · Molecular Immunology · doi:10.1016/j.molimm.2014.01.014 · Cited by 101 · see citing works
Prognostic and therapeutic role of tumor-infiltrating lymphocyte subtypes in breast cancer
Nelson, M. A., Ngamcherdtrakul, W., Luoh, S.-W., & Yantasee, W. (2021) · Cancer Metastasis Review · doi:10.1007/s10555-021-09968-0 · Cited by 99 · see citing works
Regulatory B cells in human inflammatory and autoimmune diseases: from mouse models to clinical research.
Miyagaki, T., Fujimoto, M., & Sato, S. (2015) · International Immunology · doi:10.1093/intimm/dxv026 · Cited by 99 · see citing works
Donor-derived regulatory B cells are important for suppression of murine sclerodermatous chronic graft-versus-host disease.
Huu, D. L., Matsushita, T., Jin, G., Hamaguchi, Y., Hasegawa, M., Takehara, K., Tedder, T., & Fujimoto, M. (2013) · Blood · doi:10.1182/blood-2012-11-465658 · Cited by 97 · see citing works
The immunomodulatory properties of the CD5 lymphocyte receptor in health and disease
Soldevila, G., Raman, C., & Lozano, F. (2011) · Current Opinion in Immunology · doi:10.1016/j.coi.2011.03.003 · Cited by 97 · see citing works
“IL-10 producing B-cells have an important role in controlling mouse models of autoimmune diseases, such as EAE [34], collagen-induced arthritis (CIA) [35], inflammatory bowel disease (IBD) [36], contact hypersensivity (CHS) [33 ] and SLE [37].”
MethodInfluential
Schistosome egg antigens, including the glycoprotein IPSE/alpha-1, trigger the development of regulatory B cells
Haeberlein, S., Obieglo, K., Ozir-Fazalalikhan, A., Chayé, M. A. M., Veninga, H., van der Vlugt, L. E. P. M., Voskamp, A., Boon, L., den Haan, J. M. M., Westerhof, L. B., et al. (2017) · PLOS Pathogens · doi:10.1371/journal.ppat.1006539 · Cited by 96 · see citing works
Excessive CD11c + Tbet + B cells promote aberrant T FH differentiation and affinity-based germinal center selection in lupus
Zhang, W., Zhang, H., Liu, S., Xia, F., Kang, Z., Zhang, Y., Liu, Y., Xiao, H. Q., Chen, L., Huang, C., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1901340116 · Cited by 103 · see citing works
Transcriptional regulation of the anti-inflammatory cytokine IL-10 in acquired immune cells
Kubo, M., & Motomura, Y. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00275 · Cited by 99 · see citing works
B cell immunosenescence: different features of naive and memory B cells in elderly
Buffa, S., Bulati, M., Pellicanò, M., Dunn‐Walters, D. K., Wu, Y.-C. B., Candore, G., Vitello, S., Caruso, C., & Colonna‐Romano, G. (2011) · Biogerontology · doi:10.1007/s10522-011-9353-4 · Cited by 104 · see citing works
“It has been demonstrated (Lampropoulou et al. 2008) that TLR2, TLR4 and TLR9 engagement induces IL-10”
Pathogen manipulation of B cells: the best defence is a good offence
Nothelfer, K., Sansonetti, P., & Phalipon, A. (2015) · Nature Reviews Microbiology · doi:10.1038/nrmicro3415 · Cited by 94 · see citing works
Insights into the heterogeneity of human B cells: diverse functions, roles in autoimmunity, and use as therapeutic targets
Anolik, J., Looney, R. J., Lund, F., Randall, T., & Sanz, I. (2009) · Immunologic research · doi:10.1007/s12026-009-8096-7 · Cited by 92 · see citing works
“B cells may also directly suppress Th1 and Th17-mediated diseases (37).”
Background
A Case for Regulatory B Cells in Controlling the Severity of Autoimmune-Mediated Inflammation in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis
Ray, A., Mann, M. K., Basu, S., & Dittel, B. (2010) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2010.10.037 · Cited by 88 · see citing works
“Furthermore, signaling through either TLR4 (LPS) or TLR9 (CpG) induced the expression of IL-10 in B cells, but only TLR2/4 expression by B cells regulated recovery from EAE (Lampropoulou et al., 2008).”
Influential
Th17 cells in central nervous system autoimmunity
Sie, C., Korn, T., & Mitsdoerffer, M. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2014.03.009 · Cited by 91 · see citing works
Targeting Poly(I:C) to the TLR3-Independent Pathway Boosts Effector CD8 T Cell Differentiation through IFN-α/β
Ngoi, S. M., Tovey, M. G., & Vella, A. T. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.11.7670 · Cited by 78 · see citing works
“Similarly, TLR ligand-activated B cells antagonized IFN- production by CD4 T cells through an IL-10-dependent mechanism (53).”
Background
Regulatory B cells: Phenotype, function and role in transplantation.
Wortel, C., & Heidt, S. (2017) · Transplant Immunology · doi:10.1016/j.trim.2017.02.004 · Cited by 85
Regulatory functions of B cells in allergic diseases
Braza, F., Chesne, J., Castagnet, S., Magnan, A., & Brouard, S. (2014) · Allergy. European Journal of Allergy and Clinical Immunology · doi:10.1111/all.12490 · Cited by 83 · see citing works
Role for MyD88, TLR2 and TLR9 but Not TLR1, TLR4 or TLR6 in Experimental Autoimmune Encephalomyelitis
Miranda-Hernandez, S., Gerlach, N., Fletcher, J., Biros, E., Mack, M., Körner, H., & Baxter, A. (2011) · Journal of Immunology · doi:10.4049/jimmunol.1001992 · Cited by 83 · see citing works
“The dependence of EAE induction on MyD88 signaling has been reported previously (32, 33, 67), as has the lack of an EAE phenotype in TLR6-deficient mice (33); the role of TLR1 in EAE has”
Background
Commensal gut flora and brain autoimmunity: a love or hate affair?
Berer, K., & Krishnamoorthy, G. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-0949-9 · Cited by 82 · see citing works
Regulation of autoimmune encephalomyelitis by toll-like receptors.
Marta, M., Meier, U., & Lobell, A. (2009) · Autoimmunity Reviews · doi:10.1016/j.autrev.2009.01.006 · Cited by 81 · see citing works
“In another study, clinical signs of MOG35–55-induced EAE in mice with TLR9−/− B cells were similar to mice with TLR9 B cells [24].”
BackgroundResult
B cells and Immunological Tolerance
Orduño, N. M., Quach, T., & Sanz, I. (2009) · Journal of Investigative Dermatology · doi:10.1038/jid.2008.240 · Cited by 81 · see citing works
“Inhibition of Th1 and Th17 cells (TLR-mediated) (101)”
BackgroundInfluential
Immunological Perspective: Helicobacter pylori Infection and Gastritis
Yang, H., & Hu, B. (2022) · Mediators of Inflammation · doi:10.1155/2022/2944156 · Cited by 85 · see citing works
“TLR signaling in B cells inhibits inflammatory T cell response (both Th1 and Th17 cells), which can be controlled by TLR agonists [57].”
Background
B Cells Producing Type I IFN Modulate Macrophage Polarization in Tuberculosis
Bénard, A., Sakwa, I., Schierloh, P., Colom, A., Mercier, I., Tailleux, L., Jouneau, L., Boudinot, P., Saati, T. A., Lang, R., et al. (2017) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201707-1475oc · Cited by 88 · see citing works
“Because MyD88 signaling controls the production of IL-6 and IL-10 by B cells (49), we cannot exclude that these cytokines play a part in the observed phenotype.”
BackgroundSelf-citation
A regulatory CD9+ B‐cell subset inhibits HDM‐induced allergic airway inflammation
Braza, F., Chesné, J., Durand, M., Dirou, S., Brosseau, C., Mahay, G., Cheminant, M., Magnan, A., & Brouard, S. (2015) · Allergy. European Journal of Allergy and Clinical Immunology · doi:10.1111/all.12697 · Cited by 79 · see citing works
“Moreover, IL-10-secreting B cells can inhibit the production of IL-6 and IL-23 by dendritic cells in vitro, which might explain how Bregs can reduce TH17 responses in vivo (42).”
Background
B cells expressing CD11b effectively inhibit CD4+ T‐cell responses and ameliorate experimental autoimmune hepatitis in mice
Liu, X., Jiang, X., Liu, R.-H., Wang, L., Qian, T., Zheng, Y.-J., Deng, Y.-T., Huang, E., Xu, F.-K., Wang, J.-Y., et al. (2015) · Hepatology · doi:10.1002/hep.28001 · Cited by 78 · see citing works
Emerging concepts in autoimmune encephalomyelitis beyond the CD4/TH1 paradigm
Batoulis, H., Addicks, K., & Küerten, S. (2010) · Annals of Anatomy - Anatomischer Anzeiger · doi:10.1016/j.aanat.2010.06.006 · Cited by 71 · see citing works
B-cell linker protein expression contributes to controlling allergic and autoimmune diseases by mediating IL-10 production in regulatory B cells.
Jin, G., Hamaguchi, Y., Matsushita, T., Hasegawa, M., Huu, D. L., Ishiura, N., Naka, K., Hirao, A., Takehara, K., & Fujimoto, M. (2013) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2013.01.044 · Cited by 77 · see citing works
“Nonetheless, activation through BCR and CD40 is also needed for the induction of IL-10–producing regulatory B cells to optimally suppress autoimmunity.(2,13,14,31) Thus, a 2-step activation model has been proposed.”
BackgroundMethod
Pathogenic and Protective Functions of TNF in Neuroinflammation Are Defined by Its Expression in T Lymphocytes and Myeloid Cells
Kruglov, A., Lampropoulou, V., Fillatreau, S., & Nedospasov, S. A. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100663 · Cited by 75 · see citing works
“Mice were scored daily, as described elsewhere (18).”
MethodSelf-citation

Authors: Lampropoulou, V., Hoehlig, K., Roch, T., Neves, P., Gómez, E. C., Sweenie, C. H., Hao, Y., Freitas, A. A., Steinhoff, U., Anderton, S. M., & Fillatreau, S.
Affiliations: German Rheumatism Research Centre (DE)
Deutsches Rheuma-ForschungsZentrum , Berlin ,
University of Edinburgh (GB)
Centre National de la Recherche Scientifique (FR)
Unité de Recherche Associée Centre National de la Recherche Scientifique 1961, Institut Pasteur , Paris ,
Max Planck Institute for Infection Biology (DE)
ORCID: Lampropoulou, Vicky
Hoehlig, Kai
Roch, Toralf
Hao, Yi
Steinhoff, Ulrich
Fillatreau, Simon
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 2008-04-01
Volume: 180
Issue: 7
Pages: 4763-4773
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.180.7.4763
OpenAlex: W1918941126
Cited by: 436
References: 81
Citations by year: 2026: 11 · 2025: 7 · 2024: 11 · 2023: 13 · 2022: 17 · 2021: 23 · 2020: 13 · 2019: 17 · 2018: 24 · 2017: 24 · 2016: 41 · 2015: 31 · 2014: 34 · 2013: 40 · 2012: 33
FWCI: 13.45
Type: journal article
Language: en
Open access: closed
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: The Journal of Immunology (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion)
Max Planck Institute for Plasma Physics (submittedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
Keywords: MyD88, T cell-mediated autoimmunity, experimental autoimmune encephalomyelitis, Th17 cells, Th1 cells, B cell suppression, TLR agonists, dendritic cells, macrophages
MeSH terms: Animals, B-Lymphocytes, Dendritic Cells, Encephalomyelitis, Autoimmune, Experimental, Lymphocyte Activation, Mice, Inbred C57BL, Mycobacterium tuberculosis, T-Lymphocytes, Signal Transduction, Autoimmunity, Interleukin-10, Mice, Knockout, Toll-Like Receptors, Mice, Myeloid Differentiation Factor 88

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TLR-Activated B Cells Suppress T Cell-Mediated Autoimmunity

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