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

The DOI matches its Crossref record; 79 of the 81 references it cites were found in a registry or an index.

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·2008·The Journal of Immunology

DOI 10.4049/jimmunol.180.7.4763

Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.4049/jimmunol.180.7.4763

Cites

79 of 79 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

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×
“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×
“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×
“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×
“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×
“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×
“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×
“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 2,723 · cited 1×
“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 2,598 · cited 1×
“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. M. (2003) · Science · doi:10.1126/science.1078231 · Cited by 2,000 · cited 3×
“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×
“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 1,896 · cited 16×
“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×
“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×
“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×
“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×
“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×
“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×
“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×
“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×
“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×
“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×
“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×
“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
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×
“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×
“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×
“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×
“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
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×
“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
Cutting Edge: MyD88 Is Required for Resistance to Toxoplasma gondii Infection and Regulates Parasite-Induced IL-12 Production by Dendritic Cells
Scanga, C. A., Aliberti, J., Jankovic, D. L., Tilloy, F., Bennouna, S., Denkers, E., Medzhitov, R. M., & Sher, A. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.12.5997 · Cited by 500 · 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
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×
“They also prevent autoimmune diabetes with a mechanism that possibly involves TGF- and FasL (59).”
Background
B cells inhibit induction of T cell-dependent tumor immunity
Qin, Z., Richter, G. H. S., Schüler, T., Ibe, S., Cao, X., & Blankenstein, T. J. F. (1998) · Nature Medicine · doi:10.1038/nm0598-627 · Cited by 418 · cited 1×
“Furthermore, B cells can limit antitumor immunity (70).”
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×
“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
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×
“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×
“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×
“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×
“B cells may also suppress pathogenic T cells by interacting with regulatory T cells (60), which are also necessary for disease resolution (61).”
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×
“IF N - γ (n g/ m l) MOG(35-55) (μg/ml) 0 20 30 40 10 0 20 40 50”
BackgroundMethodInfluential
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 300 · 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
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×
“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×
“For instance, the tropical helminth Schistosoma mansoni induces IL-10 production by B cells (78), and thereby protects mice from anaphylaxis (79).”
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 288 · cited 16×
“IF N - γ (n g/ m l) MOG(35-55) (μg/ml) 0 20 30 40 10 0 20 40 50”
BackgroundMethodInfluential
Critical Roles of Myeloid Differentiation Factor 88-Dependent Proinflammatory Cytokine Release in Early Phase Clearance of Listeria monocytogenes in Mice
Seki, E., Tsutsui, H., Tsuji, N. M., Hayashi, N., Adachi, K., Nakano, H., Futatsugi‐Yumikura, S., Takeuchi, O., Hoshino, K., Akira, S., et al. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.7.3863 · Cited by 276 · cited 1×
“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×
“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
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×
“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×
“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×
“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
MyD88-Dependent but Toll-Like Receptor 2-Independent Innate Immunity to Listeria : No Role for Either in Macrophage Listericidal Activity
Edelson, B. T., & Unanue, E. R. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.7.3869 · Cited by 234 · cited 1×
“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
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×
“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×
“TLR play crucial roles in host defense mechanisms (7).”
Background
Recognition of fungal pathogens by Toll-like receptors
Netea, M. G., de Graaf, C., van der Meer, J. W. M., & Kullberg, B. J. (2004) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-004-1192-7 · Cited by 172 · cited 1×
“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
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 170 · cited 16×
“IF N - γ (n g/ m l) MOG(35-55) (μg/ml) 0 20 30 40 10 0 20 40 50”
BackgroundMethodInfluential
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
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×
“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×
“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 152
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×
“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
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×
“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×
“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
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 91
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×
“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×
“CD8 DC can protect mice from arthritis after CpG administration (29).”
Background
A Role for Inflammatory Mediators in the Induction of Immunoregulatory B Cells
Matsumura, Y., Byrne, S. N., Nghiem, D. X., Miyahara, Y., & Ullrich, S. E. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.7.4810 · Cited by 82 · cited 1×
“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×
“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×
“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×
“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

Flagged first, then by citations

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

Research works printed but not linked: 80

1997, Nature, 394
1998, Science, 2085
1999, J. Immunol., 3920
2007, Semin. Immunol., 33
2006, Curr. Pharm. Des., 4195
2005, Int. Immunol., 1409
2007, Cell. Microbiol., 1891
2000, J. Immunol., 5392
2004, J. Immunol., 4463
2002, J. Immunol., 5997
2004, J. Clin. Invest., 1790
1996, Cell, 973
2002, Annu. Rev. Immunol., 197
2004, Science, 1014
1995, Infect. Immun., 3674
1995, Annu. Rev. Immunol., 437
2002, J. Immunol., 3863
2002, J. Immunol., 3869
1970, Science, 1042
1989, Cold Spring Harbor Symp. Quant. Biol., 1
1994, Immunity, 327
2003, Science, 1033
1999, Nat. Med., 702
2000, J. Immunol., 5683
2005, Nat. Med., 138
2007, Eur. J. Immunol., 2734
2007, Arthritis Rheum., 1618
2007, J. Neuroimmunol., 32
2007, J. Exp. Med., 1911
2000, J. Immunol., 6148
2002, Gastroenterology, 1428
1996, J. Exp. Med., 1389
2006, Immunity, 417
2006, Arthritis Rheum., 336
2007, Ann. Rheum. Dis., 905
2002, Nat. Immunol., 944
2002, Immunity, 219
2003, J. Exp. Med., 489
2004, J. Immunol., 3422
2007, J. Immunol., 6092
2003, J. Exp. Med., 195
1993, J. Immunol., 4371
2005, Nat. Immunol., 1133
2006, J. Clin. Invest., 456
2004, Cell, 229
2000, J. Exp. Med., 475
2005, J. Immunol., 4761
2007, J. Exp. Med., 105
2005, J. Immunol., 5601
2006, Eur. J. Immunol., 12
2007, J. Immunol., 7868
2006, Nature, 235
2007, Nature, 484
2007, Nat. Immunol., 1390
1999, J. Immunol., 4284
1998, J. Exp. Med., 537
2000, J. Neuroimmunol., 55
2003, J. Immunol., 5897
2001, J. Immunol., 1081
2007, J. Immunol., 3447
2005, J. Immunol., 3025
2007, Proc. Natl. Acad. Sci. USA, 14080
2006, J. Immunol., 4810
2002, Annu. Rev. Immunol., 709
2005, J. Exp. Med., 1715
2001, J. Exp. Med., 863
2001, Eur. J. Immunol., 3388
2006, J. Immunol., 1670
2005, Hepatology, 724
1998, Nat. Med., 627
2006, Neurology, 652
2001, Nat. Rev. Immunol., 20
1981, Acta Neurol. Scand., 131
1999, Neurology, 1588
1958, Nature, 1106
1992, J. Autoimmun., 675
2003, Clin. Diagn. Lab. Immunol., 564
1994, Proc. Natl. Acad. Sci. USA, 18
2004, J. Immunol., 6346
2002, N. Engl. J. Med., 911

Sorted by citations

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 3,058
Immune Regulatory Function of B Cells
Mauri, C., & Bosma, A. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-074934 · Cited by 1,298
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
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
Self-citation
B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6–producing B cells
Barr, T. A., Shen, P., Brown, S. L., Lampropoulou, V., Roch, T., Lawrie, S., Fan, B., O’Connor, R. A., Anderton, S. M., Bar‐Or, A., et al. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20111675 · Cited by 673
“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

See all 436

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 › Clinical Neurology › 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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

TLR-Activated B Cells Suppress T Cell-Mediated Autoimmunity

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Metadata

Record

About these checks