Late Developmental Plasticity in the T Helper 17 Lineage

Lee, Yun Kyung; Turner, Henrietta; Maynard, Craig L.; Oliver, James R.; Chen, Dongquan; Elson, Charles O.; Weaver, Casey T.

doi:10.1016/j.immuni.2008.11.005

Cited by 1,053Psoriasis: Treatment and PathogenesisT-cell and B-cell ImmunologyCytokine Signaling Pathways and Interactions

Late Developmental Plasticity in the T Helper 17 Lineage

Open access

Lee, Yun Kyung, Turner, Henrietta, Maynard, Craig L., Oliver, James R., Chen, Dongquan, Elson, Charles O., Weaver, Casey T.·2009·Immunity

DOI 10.1016/j.immuni.2008.11.005PMC PMC3607320

Open this paper in CoChat — free account Open PDF

Abstract

Development of T helper (Th) 17 cells requires transforming growth factor (TGF)-beta and interleukin (IL)-6 and is independent of the Th1 pathway. Although T cells that produce interferon (IFN)-gamma are a recognized feature of Th17 cell responses, mice deficient for STAT4 and T-bet-two prototypical Th1 transcription factors-are protected from autoimmunity associated with Th17 pathogenesis. To examine the fate and pathogenic potential of Th17 cells and origin of IFN-gamma-producing T cells that emerge during Th17 immunity, we developed IL-17F reporter mice that identify cells committed to expression of IL-17F and IL-17A. Th17 cells required TGF-beta for sustained expression of IL-17F and IL-17A. In the absence of TGF-beta, both IL-23 and IL-12 acted to suppress IL-17 and enhance IFN-gamma production in a STAT4- and T-bet-dependent manner, albeit with distinct efficiencies. These results support a model of late Th17 developmental plasticity with implications for autoimmunity and host defense.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1016/j.immuni.2008.11.005

Cites

62 of 62 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

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?

Ongoing IL-6 signaling is indispensable and foundational, acting upstream of IL-23 via its unique function to sustain RORγt expression and thereby IL-23R expression.
“Although it has been reported that IL-23 signaling is important for the maintenance of Th17 cells (18, 19, 21), we find that ongoing IL-6 signaling is indispensable and foundational, acting upstream of IL-23 via its unique function to sustain RORγt expression and thereby IL-23R expression.”
From T H 17 cells require ongoing classic IL-6 receptor signaling to retain transcriptional and functional identity (2020) · cites this paper as [19]
The citation attaches to the reported importance of IL-23 signaling for Th17 maintenance, not to the citing authors’ finding about ongoing IL-6 signaling. In Results (‘TGF-β Is Required for Maintenance of IL-17 Expression by Th17 Cells’), the source says the opposite: IL-23 appears dispensable for Th17 maintenance, whereas continuous TGF-β signaling is needed to maintain IL-17 expression. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measured
Th17 cells show substantially greater plasticity than Th1 and Th2 cells.
“In contrast to Th1 and Th2 cells, Th17 cells show substantially greater plasticity (19, 23, 65).”
From T H 17 cells require ongoing classic IL-6 receptor signaling to retain transcriptional and functional identity (2020) · cites this paper as [19]
The Results section (‘TGF-β Is Required for Maintenance of IL-17 Expression by Th17 Cells’; page unavailable) says Th17 cells appear more plastic than Th1 cells in late-stage cytokine expression. The copy does not make the same plasticity comparison with Th2 cells; searching for ‘Th2’ found discussion of its differentiation factors and cytokines, not that comparison. (LLM, conf=0.86)
Experimental — accuracy not yet measured
IL-23 has been reported to be a trophic factor for Th17 cells, but IL-23 signaling also promotes the transdifferentiation of Th17 cells to Th1-like cells.
“IL-23 has been reported to be a trophic factor for Th17 cells (19, 23, 65), but IL-23 signaling also promotes the transdifferentiation of Th17 cells to Th1-like cells (19, 26)”
From T H 17 cells require ongoing classic IL-6 receptor signaling to retain transcriptional and functional identity (2020) · cites this paper as [19]
The Introduction reports that IL-23 had been speculated to enhance or maintain the Th17 phenotype, but the paper's Results find IL-23 dispensable for Th17 maintenance. The Results also show IL-23 promoting a shift toward IFN-γ-producing, Th1-like progeny, specifically when TGF-β is low or absent; the citing sentence omits that condition. (LLM, conf=0.85)
Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

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 · see citing works
The Orphan Nuclear Receptor RORγt Directs the Differentiation Program of Proinflammatory IL-17+ T Helper Cells
Ivanov, I. I., McKenzie, B. S., Zhou, L., Tadokoro, C. E., Lepelley, A., Lafaille, J. J., Cua, D. J., & Littman, D. R. (2006) · Cell · doi:10.1016/j.cell.2006.07.035 · Cited by 5,145 · see citing works
Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages
Harrington, L. E., Hatton, R. D., Mangan, P. R., Turner, H., Murphy, T. L., Murphy, K. M., & Weaver, C. T. (2005) · Nature Immunology · doi:10.1038/ni1254 · Cited by 4,742 · see citing works
Self-citation
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 · see citing works
IL-23 drives a pathogenic T cell population that induces autoimmune inflammation
Langrish, C. L., Chen, Y., Blumenschein, W. M., Mattson, J., Basham, B., Sedgwick, J. D., McClanahan, T., Kastelein, R. A., & Cua, D. J. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20041257 · Cited by 4,099 · see citing works
TGFβ in the Context of an Inflammatory Cytokine Milieu Supports De Novo Differentiation of IL-17-Producing T Cells
Veldhoen, M., Hocking, R. J., Atkins, C. J., Locksley, R. M., & Stockinger, B. (2006) · Immunity · doi:10.1016/j.immuni.2006.01.001 · Cited by 3,605 · see citing works
Transforming growth factor-β induces development of the TH17 lineage
Mangan, P. R., Harrington, L. E., O'Quinn, D. B., Helms, W. S., Bullard, D. C., Elson, C. O., Hatton, R. D., Wahl, S. M., Schoeb, T. R., & Weaver, C. T. (2006) · Nature · doi:10.1038/nature04754 · Cited by 3,087 · see citing works
Self-citation
Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain
Cua, D. J., Sherlock, J., Chen, Y., Murphy, C. A., Joyce, B., Seymour, B., Lucian, L., To, W., Kwan, S., Churakova, T., et al. (2003) · Nature · doi:10.1038/nature01355 · Cited by 2,906 · see citing works
Novel p19 Protein Engages IL-12p40 to Form a Cytokine, IL-23, with Biological Activities Similar as Well as Distinct from IL-12
Oppmann, B., Lesley, R., Blom, B., Timans, J. C., Xu, Y., Hunte, B., Vega, F., Yu, N., Wang, J., Singh, K. P., et al. (2000) · Immunity · doi:10.1016/s1074-7613(00)00070-4 · Cited by 2,819 · see citing works
Interleukin-17 Family Members and Inflammation
Kolls, J. K., & Lindén, A. (2004) · Immunity · doi:10.1016/j.immuni.2004.08.018 · Cited by 2,371 · see citing works
IL-6 programs TH-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways
Zhou, L., Ivanov, I. I., Spolski, R. J., Min, R., Shenderov, K., Egawa, T., Levy, D. E., Leonard, W. J., & Littman, D. R. (2007) · Nature Immunology · doi:10.1038/ni1488 · Cited by 2,134 · see citing works
Interleukin-22, a TH17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis
Zheng, Y., Danilenko, D., Valdez, P., Kasman, I., Eastham-Anderson, J., Wu, J., & Ouyang, W. (2007) · Nature · doi:10.1038/nature05505 · Cited by 2,034 · see citing works
Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens
Zheng, Y., Valdez, P. A., Danilenko, D. M., Hu, Y., Susan, M. L., Gong, Q., Abbas, A. R., Modrusan, Z. D., Ghilardi, N., de Sauvage, F. J., et al. (2008) · Nature Medicine · doi:10.1038/nm1720 · Cited by 1,910 · see citing works
Phenotypic and functional features of human Th17 cells
Annunziato, F., Cosmi, L., Santarlasci, V., Maggi, L., Liotta, F., Mazzinghi, B., Parente, E., Filì, L., Ferri, S., Frosali, F., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070663 · Cited by 1,861 · see citing works
Interleukin-23 Promotes a Distinct CD4 T Cell Activation State Characterized by the Production of Interleukin-17
Aggarwal, S., Ghilardi, N., Xie, M.-H., de Sauvage, F. J., & Gurney, A. L. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m207577200 · Cited by 1,848 · see citing works
IL-17 family cytokines and the expanding diversity of effector T cell lineages
Weaver, C. T., Hatton, R. D., Mangan, P. R., & Harrington, L. E. (2007) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141557 · Cited by 1,842 · see citing works
Self-citation
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 · see citing works
Divergent Pro- and Antiinflammatory Roles for IL-23 and IL-12 in Joint Autoimmune Inflammation
Murphy, C. A., Langrish, C. L., Chen, Y., Blumenschein, W., McClanahan, T., Kastelein, R. A., Sedgwick, J. D., & Cua, D. J. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030896 · Cited by 1,669 · see citing works
T Helper 17 Lineage Differentiation Is Programmed by Orphan Nuclear Receptors RORα and RORγ
Yang, X. O., Pappu, B. P., Nurieva, R., Akimzhanov, A., Kang, H. S., Chung, Y., Ma, L., Shah, B., Panopoulos, A. D., Schluns, K. S., et al. (2008) · Immunity · doi:10.1016/j.immuni.2007.11.016 · Cited by 1,605 · see citing works
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 · see citing works
Interleukin-2 Signaling via STAT5 Constrains T Helper 17 Cell Generation
Laurence, A., Tato, C. M., Davidson, T. S., Kanno, Y., Chen, Z., Yao, Z., Blank, R. B., Meylan, F., Siegel, R., Hennighausen, L., et al. (2007) · Immunity · doi:10.1016/j.immuni.2007.02.009 · Cited by 1,507 · see citing works
STAT3 Regulates Cytokine-mediated Generation of Inflammatory Helper T Cells
Yang, X. O., Panopoulos, A. D., Nurieva, R., Chang, S. H., Wang, D., Watowich, S. S., & Dong, C. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.c600321200 · Cited by 1,494 · see citing works
Essential autocrine regulation by IL-21 in the generation of inflammatory T cells
Nurieva, R., Yang, X. O., Martinez, G., Zhang, Y., Panopoulos, A. D., Ma, L., Schluns, K., Tian, Q., Watowich, S. S., Jetten, A. M., et al. (2007) · Nature · doi:10.1038/nature05969 · Cited by 1,466 · see citing works
IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challenge
Khader, S. A., Bell, G. K., Pearl, J. E., Fountain, J. J., Rangel‐Moreno, J., Cilley, G. E., Shen, F., Eaton, S. M., Gaffen, S. L., Swain, S. L., et al. (2007) · Nature Immunology · doi:10.1038/ni1449 · Cited by 1,442 · see citing works
Th17: An Effector CD4 T Cell Lineage with Regulatory T Cell Ties
Weaver, C. T., Harrington, L. E., Mangan, P. R., Gavrieli, M., & Murphy, K. M. (2006) · Immunity · doi:10.1016/j.immuni.2006.06.002 · Cited by 1,422 · see citing works
Self-citation
A Receptor for the Heterodimeric Cytokine IL-23 Is Composed of IL-12Rβ1 and a Novel Cytokine Receptor Subunit, IL-23R
Parham, C. L., Chirica, M., Timans, J., Vaisberg, E., Travis, M. A., Cheung, J., Pflanz, S., Zhang, R. V., Singh, K. P., Vega, F., et al. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.11.5699 · Cited by 1,297 · see citing works
Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE).
Ferber, I., Brocke, S., Taylor-Edwards, C., Ridgway, W., Dinisco, C., Steinman, L., Dalton, D., & Fathman, C. (1996) · Journal of Immunology · doi:10.4049/jimmunol.156.1.5 · Cited by 1,088 · see citing works
Phenotypically distinct subsets of CD4 + T cells induce or protect from chronic intestinal inflammation in C. B-17 scid mice
Powrie, F., Leach, M. W., Mauze, S., Caddie, L. B., & Coffman, R. L. (1993) · International Immunology · doi:10.1093/intimm/5.11.1461 · Cited by 1,078 · see citing works
A critical role for transforming growth factor-beta but not interleukin 4 in the suppression of T helper type 1-mediated colitis by CD45RB(low) CD4+ T cells.
Powrie, F. M., Carlino, J. A., Leach, M. W., Mauze, S., & Coffman, R. L. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.6.2669 · Cited by 894 · see citing works
Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17–producing T cells
Batten, M., Li, J., Yi, S., Kljavin, N. M., Danilenko, D. M., Lucas, S., Lee, J., de Sauvage, F. J., & Ghilardi, N. (2006) · Nature Immunology · doi:10.1038/ni1375 · Cited by 815 · see citing works
Understanding the IL-23–IL-17 immune pathway
McKenzie, B. S., Kastelein, R. A., & Cua, D. J. (2005) · Trends in Immunology · doi:10.1016/j.it.2005.10.003 · Cited by 761 · see citing works
Differentiation and function of Th17 T cells
Stockinger, B., & Veldhoen, M. (2007) · Current Opinion in Immunology · doi:10.1016/j.coi.2007.04.005 · Cited by 716 · see citing works
Th17 Cell Differentiation: The Long and Winding Road
McGeachy, M. J., & Cua, D. J. (2008) · Immunity · doi:10.1016/j.immuni.2008.03.001 · Cited by 700 · see citing works
IFN-gamma plays a critical down-regulatory role in the induction and effector phase of myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis
Willenborg, D. O., Fordham, S. A., Bernard, C. C. A., Cowden, W. B., & Ramshaw, I. A. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.157.8.3223 · Cited by 636 · see citing works
Regulatory interactions between CD45RBhigh and CD45RBlow CD4+ T cells are important for the balance between protective and pathogenic cell-mediated immunity.
Powrie, F., Correa-Oliveira, R., Mauze, S., & Coffman, R. L. (1994) · The Journal of experimental medicine · doi:10.1084/jem.179.2.589 · Cited by 613 · see citing works
The Transcription Factor T-bet Regulates Mucosal T Cell Activation in Experimental Colitis and Crohn's Disease
Neurath, M. F., Weigmann, B., Finotto, S., Glickman, J. N., Nieuwenhuis, E. E. S., Iijima, H., Mizoguchi, A., Mizoguchi, E., Mudter, J., Galle, P. R., et al. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20011956 · Cited by 606 · see citing works
Regulatory T cells expressing interleukin 10 develop from Foxp3+ and Foxp3− precursor cells in the absence of interleukin 10
Maynard, C. L., Harrington, L. E., Janowski, K. M., Oliver, J. R., Zindl, C. L., Rudensky, A. Y., & Weaver, C. T. (2007) · Nature Immunology · doi:10.1038/ni1504 · Cited by 599 · see citing works
Self-citation
Cutting Edge: An In Vivo Requirement for STAT3 Signaling in TH17 Development and TH17-Dependent Autoimmunity
Harris, T. J., Grosso, J. F., Yen, H., Xin, H., Kortylewski, M., Albesiano, E., Hipkiss, E. L., Getnet, D., Goldberg, M. V., Maris, C. H., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.7.4313 · Cited by 585 · see citing works
Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis
Chen, Y. (2006) · Journal of Clinical Investigation · doi:10.1172/jci25308 · Cited by 554 · see citing works
Stat3 and Stat4 Direct Development of IL-17-Secreting Th Cells
Mathur, A. N., Chang, H., Zisoulis, D. G., Stritesky, G. L., Yu, Q., O’Malley, J. T., Kapur, R., Levy, D. E., Kansas, G. S., & Kaplan, M. H. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.8.4901 · Cited by 548 · see citing works
IL-17s adopt a cystine knot fold: structure and activity of a novel cytokine, IL-17F, and implications for receptor binding
Hymowitz, S. G., Filvaroff, E. H., Yin, J., Lee, J., Cai, L., Risser, P., Maruoka, M., Mao, W., Foster, J., Kelley, R. F., et al. (2001) · The EMBO Journal · doi:10.1093/emboj/20.19.5332 · Cited by 548 · see citing works
Loss of T-bet, But Not STAT1, Prevents the Development of Experimental Autoimmune Encephalomyelitis
Bettelli, E., Sullivan, B., Szabo, S. J., Sobel, R., Glimcher, L., & Kuchroo, V. (2004) · Journal of Experimental Medicine · doi:10.1084/jem.20031819 · Cited by 546 · see citing works
The IL-27R (WSX-1) Is Required to Suppress T Cell Hyperactivity during Infection
Villarino, A. V., Hibbert, L., Lieberman, L. A., Wilson, E. H., Mak, T. W., Yoshida, H., Kastelein, R. A., Saris, C. J. M., & Hunter, C. A. (2003) · Immunity · doi:10.1016/s1074-7613(03)00300-5 · Cited by 484 · see citing works
Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12.
Becher, B., Durell, B., & Noelle, R. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15751 · Cited by 481 · see citing works
Monoclonal Anti–Interleukin 23 Reverses Active Colitis in a T Cell–Mediated Model in Mice
Elson, C. O., Cong, Y., Weaver, C. T., Schoeb, T. R., McClanahan, T. K., Fick, R. B., & Kastelein, R. A. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.03.104 · Cited by 453 · see citing works
Self-citation
Role of Th1 and Th17 cells in organ-specific autoimmunity
Dardalhon, V., Korn, T., Kuchroo, V. K., & Anderson, A. C. (2008) · Journal of Autoimmunity · doi:10.1016/j.jaut.2008.04.017 · Cited by 450 · see citing works
Interleukin-23 Restrains Regulatory T Cell Activity to Drive T Cell-Dependent Colitis
Ízcue, A., Hüe, S., Buonocore, S. M., Arancibia-Cárcamo, C. V., Ahern, P. P., Iwakura, Y., Maloy, K. J., & Powrie, F. M. (2008) · Immunity · doi:10.1016/j.immuni.2008.02.019 · Cited by 411 · see citing works
IL-12p35-Deficient Mice Are Susceptible to Experimental Autoimmune Encephalomyelitis: Evidence for Redundancy in the IL-12 System in the Induction of Central Nervous System Autoimmune Demyelination
Gran, B., Zhang, G., Yu, S., Li, J., Chen, X., Ventura, E. S., Kamoun, M., & Rostami, A. M. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.12.7104 · Cited by 405 · see citing works
Cutting Edge: TGF-β Inhibits Th Type 2 Development Through Inhibition of GATA-3 Expression
Gorelik, L., Fields, P. E., & Flavell, R. A. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.9.4773 · Cited by 391 · see citing works
An IL-17F/A Heterodimer Protein Is Produced by Mouse Th17 Cells and Induces Airway Neutrophil Recruitment
Liang, S. C., Long, A. J., Bennett, F., Whitters, M. J., Karim, R., Collins, M. A., Goldman, S. J., Dunussi‐Joannopoulos, K., Williams, C. M. M., Wright, J. F., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.11.7791 · Cited by 371 · see citing works
Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12
Becher, B., Durell, B. G., & Noelle, R. J. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215751 · Cited by 347 · see citing works
Induction of Experimental Autoimmune Encephalomyelitis in IL-12 Receptor-β2-Deficient Mice: IL-12 Responsiveness Is Not Required in the Pathogenesis of Inflammatory Demyelination in the Central Nervous System
Zhang, G., Gran, B., Yu, S., Li, J., Siglienti, I., Chen, X., Kamoun, M., & Rostami, A. M. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.4.2153 · Cited by 305 · see citing works
Memory CD4 T cells emerge from effector T-cell progenitors
Harrington, L., Janowski, K., Oliver, J., Zajac, A., & Weaver, C. (2008) · Nature · doi:10.1038/nature06672 · Cited by 290 · see citing works
Self-citation
A novel heterodimeric cytokine consisting of IL-17 and IL-17F regulates inflammatory responses
Chang, S. H., & Dong, C. (2007) · Cell Research · doi:10.1038/cr.2007.35 · Cited by 280 · see citing works
Effect of targeted disruption of STAT4 and STAT6 on the induction of experimental autoimmune encephalomyelitis
Chitnis, T., Najafian, N., Benou, C., Salama, A. D., Grusby, M. J., Sayegh, M. H., & Khoury, S. J. (2001) · Journal of Clinical Investigation · doi:10.1172/jci12563 · Cited by 230 · see citing works
TGF-β1 Uses Distinct Mechanisms to Inhibit IFN-γ Expression in CD4+ T Cells at Priming and at Recall: Differential Involvement of Stat4 and T-bet
Lin, J. T., Martin, S. L., Xia, L., & Gorham, J. D. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.10.5950 · Cited by 163 · see citing works
IL-12– and IL-23–induced T helper cell subsets
Bettelli, E., & Kuchroo, V. K. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20042279 · Cited by 144 · see citing works
T-bet is a critical determinant in the instability of the IL-17-secreting T-helper phenotype
Mathur, A. N. (2006) · Blood · doi:10.1182/blood-2006-04-015016 · Cited by 143 · see citing works
T Helper 1 and T Helper 2 Cells Are Pathogenic in an Antigen-specific Model of Colitis
Iqbal, N., Oliver, J. R., Wagner, F. H., Lazenby, A. J., Elson, C. O., & Weaver, C. T. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.2001889 · Cited by 141 · see citing works
Self-citation
Low dose TGF-beta attenuates IL-12 responsiveness in murine Th cells.
Gorham, J. D., Guler, M. L., Fenoglio, D., Gubler, U., & MURPHY, K. M. M. (1998) · PubMed · Cited by 116 · see citing works
Low Dose TGF-β Attenuates IL-12 Responsiveness in Murine Th Cells
Gorham, J. D., Guler, M. L., Fenoglio, D., Gubler, U., & MURPHY, K. M. M. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.4.1664 · Cited by 98 · see citing works
Chromatin remodeling by the SWI/SNF‐like BAF complex and STAT4 activation synergistically induce IL‐12Rβ2 expression during human Th1 cell differentiation
Letimier, F. A., Passini, N., Gasparian, S., Bianchi, E., & Rogge, L. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601586 · Cited by 79 · see citing works

Flagged first, then by citations

Sorted by citations

Differentiation of Effector CD4 T Cell Populations
Zhu, J., Yamane, H., & Paul, W. E. (2010) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101212 · Cited by 3,452 · see citing works
Follicular Helper CD4 T Cells (T FH )
Crotty, S. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101400 · Cited by 2,738 · see citing works
Inflammatory bowel disease
Kaser, A., Zeissig, S., & Blumberg, R. S. (2010) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101225 · Cited by 1,806 · see citing works
Reciprocal interactions of the intestinal microbiota and immune system
Maynard, C. L., Elson, C. O., Hatton, R. D., & Weaver, C. T. (2012) · Nature · doi:10.1038/nature11551 · Cited by 1,598 · see citing works
Self-citation
The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing
Gaffen, S. L., Jain, R., Garg, A. V., & Cua, D. J. (2014) · Nature reviews. Immunology · doi:10.1038/nri3707 · Cited by 1,585 · see citing works
Plasticity of CD4+ T Cell Lineage Differentiation
Zhou, L., Chong, M. M. W., & Littman, D. R. (2009) · Immunity · doi:10.1016/j.immuni.2009.05.001 · Cited by 1,551 · see citing works
The Key Role of Segmented Filamentous Bacteria in the Coordinated Maturation of Gut Helper T Cell Responses
Gaboriau-Routhiau, V., Rakotobe, S., Lécuyer, E., Mulder, I., Lan, A., Bridonneau, C., Rochet, V., Pisi, A., De Paepe, M., Brandi, G., et al. (2009) · Immunity · doi:10.1016/j.immuni.2009.08.020 · Cited by 1,452 · see citing works
Immune adaptations that maintain homeostasis with the intestinal microbiota
Hooper, L. V., & Macpherson, A. J. (2010) · Nature reviews. Immunology · doi:10.1038/nri2710 · Cited by 1,455 · see citing works
CD4 + T Cells: Differentiation and Functions
Luckheeram, R. V., Zhou, R., Verma, A. D., & Xia, B. (2012) · Clinical and Developmental Immunology · doi:10.1155/2012/925135 · Cited by 1,381 · see citing works
Generation of pathogenic TH17 cells in the absence of TGF-β signalling
Ghoreschi, K., Laurence, A., Yang, X.-P., Tato, C. M., McGeachy, M. J., Konkel, J. E., Ramos, H. L., Wei, L., Davidson, T. S., Bouladoux, N., et al. (2010) · Nature · doi:10.1038/nature09447 · Cited by 1,388 · see citing works
Mechanisms Underlying Lineage Commitment and Plasticity of Helper CD4 + T Cells
O’Shea, J. J., & Paul, W. E. (2010) · Science · doi:10.1126/science.1178334 · Cited by 1,338 · see citing works
Functional Specialization of Interleukin-17 Family Members
Iwakura, Y., Ishigame, H., Saijo, S., & Nakae, S. (2011) · Immunity · doi:10.1016/j.immuni.2011.02.012 · Cited by 1,289 · see citing works
Fate mapping of IL-17-producing T cells in inflammatory responses
Hirota, K., Duarte, J. H., Veldhoen, M., Hornsby, E., Li, Y., Cua, D. J., Ahlfors, H., Wilhelm, C., Tolaini, M., Menzel, U., et al. (2011) · Nature Immunology · doi:10.1038/ni.1993 · Cited by 1,176 · see citing works
A Validated Regulatory Network for Th17 Cell Specification
Ciofani, M., Madar, A., Galan, C., Sellars, M., Mace, K., Pauli, F., Agarwal, A., Huang, W., Parkurst, C. N., Muratet, M., et al. (2012) · Cell · doi:10.1016/j.cell.2012.09.016 · Cited by 1,160 · see citing works
Proinflammatory Cytokines in the Pathogenesis of Inflammatory Bowel Diseases
Strober, W., & Fuss, I. J. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.02.016 · Cited by 1,105 · see citing works
Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology
Buonocore, S. M., Ahern, P. P., Uhlig, H. H., Ivanov, I. I., Littman, D. R., Maloy, K. J., & Powrie, F. M. (2010) · Nature · doi:10.1038/nature08949 · Cited by 1,066 · see citing works
Expanding roles for CD4+ T cells in immunity to viruses
Swain, S. L., McKinstry, K. K., & Strutt, T. M. (2012) · Nature reviews. Immunology · doi:10.1038/nri3152 · Cited by 960 · see citing works
Cross-regulation of Signaling Pathways by Interferon-γ: Implications for Immune Responses and Autoimmune Diseases
Hu, X., & Ivashkiv, L. B. (2009) · Immunity · doi:10.1016/j.immuni.2009.09.002 · Cited by 928 · see citing works
Tumor-reactive CD4(+) T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts
Quezada, S. A., Simpson, T. R., Peggs, K. S., Merghoub, T., Vider, J., Fan, X., Blasberg, R., Yagita, H., Muranski, P., Antony, P. A., et al. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20091918 · Cited by 898 · see citing works
IL-12 and IL-23 cytokines: from discovery to targeted therapies for immune-mediated inflammatory diseases
Teng, M. W. L., Bowman, E. P., McElwee, J. J., Smyth, M. J., Casanova, J., Cooper, A. M., & Cua, D. J. (2015) · Nature Medicine · doi:10.1038/nm.3895 · Cited by 877 · see citing works
Ion Channels in Innate and Adaptive Immunity
Feske, S., Wulff, H., & Skolnik, E. Y. (2015) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112212 · Cited by 764 · see citing works
Regulation of Insulin Synthesis and Secretion and Pancreatic Beta-Cell Dysfunction in Diabetes
Fu, Z., Gilbert, E. R., & Liu, D. (2012) · Current Diabetes Reviews · doi:10.2174/157339913804143225 · Cited by 882 · see citing works
Experimental Models of Inflammatory Bowel Diseases
Kiesler, P., Fuss, I. J., & Strober, W. (2015) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2015.01.006 · Cited by 719 · see citing works
Epigenetic control of T-helper-cell differentiation
Wilson, C. B., Rowell, E. A., & Sekimata, M. (2009) · Nature reviews. Immunology · doi:10.1038/nri2487 · Cited by 678 · see citing works
Progressive loss of RORγt expression confers distinct functional fates to natural killer cell receptor-expressing RORγt+ innate lymphocytes
Vonarbourg, C., Mortha, A., Bui, V. L., Hernández, P. P., Kiss, E. A., Hoyler, T., Flach, M., Bengsch, B., Thimme, R., Hölscher, C., et al. (2010) · Immunity · doi:10.1016/j.immuni.2010.10.017 · Cited by 669 · see citing works
Functional SARS-CoV-2-Specific Immune Memory Persists after Mild COVID-19
Rodda, L. B., Netland, J., Shehata, L., Pruner, K. B., Morawski, P. A., Thouvenel, C. D., Takehara, K. K., Eggenberger, J., Hemann, E. A., Waterman, H. R., et al. (2021) · Cell · doi:10.1016/j.cell.2020.11.029 · Cited by 647 · see citing works
CD27 is a thymic determinant of the balance between interferon-γ- and interleukin 17–producing γδ T cell subsets
Ribot, J. C., deBarros, A., Pang, D. J., Neves, J. F., Peperzak, V., Roberts, S. J., Girardi, M., Borst, J., Hayday, A. C., Pennington, D. J., et al. (2009) · Nature Immunology · doi:10.1038/ni.1717 · Cited by 628 · see citing works
TH17 cells in tumour immunity and immunotherapy
Zou, W., & Restifo, N. P. (2010) · Nature reviews. Immunology · doi:10.1038/nri2742 · Cited by 626 · see citing works
Single-cell genomics unveils critical regulators of Th17 cell pathogenicity
Gaublomme, J. T., Yosef, N., Lee, Y., Gertner, R. S., Yang, L. V., Wu, C., Pandolfi, P. P., Mak, T., Satija, R., Shalek, A. K., et al. (2015) · Cell · doi:10.1016/j.cell.2015.11.009 · Cited by 575 · see citing works
Self-citation
Peripheral CD4+ T‐cell differentiation regulated by networks of cytokines and transcription factors
Zhu, J., & Paul, W. E. (2010) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00951.x · Cited by 596 · see citing works
Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes.
Fu, Z., Gilbert, E. R., & Liu, D. (2013) · PubMed · Cited by 600 · see citing works
Th17 Cells Express Interleukin-10 Receptor and Are Controlled by Foxp3− and Foxp3+ Regulatory CD4+ T Cells in an Interleukin-10-Dependent Manner
Huber, S., Gagliani, N., Esplugues, E., O'Connor, W., Huber, F. J., Chaudhry, A., Kamanaka, M., Kobayashi, Y., Booth, C. J., Rudensky, A. Y., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.01.020 · Cited by 581 · see citing works
Functions of T cells in asthma: more than just TH2 cells
Lloyd, C. M., & Hessel, E. M. (2010) · Nature reviews. Immunology · doi:10.1038/nri2870 · Cited by 578 · see citing works
Decrease of Foxp3+ Treg Cell Number and Acquisition of Effector Cell Phenotype during Lethal Infection
Oldenhove, G., Bouladoux, N. J., Wohlfert, E. A., Hall, J. A., Chou, D. B., dos Santos, L. M., O’Brien, S., Blank, R. B., Lamb, E. W., Natarajan, S., et al. (2009) · Immunity · doi:10.1016/j.immuni.2009.10.001 · Cited by 578 · see citing works
Heterogeneity and plasticity of T helper cells
Zhu, J., & Paul, W. E. (2009) · Cell Research · doi:10.1038/cr.2009.138 · Cited by 564 · see citing works
Prostaglandin E2–EP4 signaling promotes immune inflammation through TH1 cell differentiation and TH17 cell expansion
Yao, C., Sakata, D., Esaki, Y., Li, Y., Matsuoka, T., Kuroiwa, K., Sugimoto, Y., & Narumiya, S. (2009) · Nature Medicine · doi:10.1038/nm.1968 · Cited by 566 · see citing works
Immunotherapy Converts Nonimmunogenic Pancreatic Tumors into Immunogenic Foci of Immune Regulation
Lutz, E. R., Wu, A. A., Bigelow, E. O., Sharma, R. B., Mo, G., Soares, K. C., Solt, S., Dorman, A., Wamwea, A., Yager, A., et al. (2014) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-14-0027 · Cited by 551 · see citing works
Preferential recruitment of interferon‐γ–expressing T H 17 cells in multiple sclerosis
Kebir, H., Ifergan, I., Alvarez, J. I., Bernard, M., Poirier, J., Arbour, N., Duquette, P., & Prat, A. (2009) · Annals of Neurology · doi:10.1002/ana.21748 · Cited by 551 · see citing works
Proinflammatory T helper type 17 cells are effective B-cell helpers
Mitsdoerffer, M., Lee, Y., Jäger, A., Kim, H.-J., Korn, T., Kolls, J. K., Cantor, H., Bettelli, E., & Kuchroo, V. K. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1009234107 · Cited by 534 · see citing works
Self-citation
The Treg/Th17 Axis: A Dynamic Balance Regulated by the Gut Microbiome
Omenetti, S., & Pizarro, T. T. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00639 · Cited by 529 · see citing works
Harnessing the plasticity of CD4+ T cells to treat immune-mediated disease
DuPage, M. J. P., & Bluestone, J. A. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2015.18 · Cited by 507 · see citing works
Helper T cell differentiation
Saravia, J., Chapman, N. M., & Chi, H. (2019) · Cellular & Molecular Immunology · doi:10.1038/s41423-019-0220-6 · Cited by 489 · see citing works
When worlds collide: Th17 and Treg cells in cancer and autoimmunity
Knochelmann, H. M., Dwyer, C. J., Bailey, S. R., Amaya, S. M., Elston, D. M., Mazza-McCrann, J. M., & Paulos, C. M. (2018) · Cellular & Molecular Immunology · doi:10.1038/s41423-018-0004-4 · Cited by 535 · see citing works
T Helper (Th) Cell Profiles in Pregnancy and Recurrent Pregnancy Losses: Th1/Th2/Th9/Th17/Th22/Tfh Cells
Wang, W., Sung, N., Gilman‐Sachs, A., & Kwak-Kim, J. Y.-H. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.02025 · Cited by 513 · see citing works
Interleukin-23 Drives Intestinal Inflammation through Direct Activity on T Cells
Ahern, P. P., Schiering, C., Buonocore, S., McGeachy, M. J., Cua, D. J., Maloy, K. J., & Powrie, F. (2010) · Immunity · doi:10.1016/j.immuni.2010.08.010 · Cited by 528 · see citing works
T-bet: a bridge between innate and adaptive immunity
Lazarevic, V., Glimcher, L. H., & Lord, G. M. (2013) · Nature Reviews Immunology · doi:10.1038/nri3536 · Cited by 486 · see citing works
Effector T cell plasticity: flexibility in the face of changing circumstances
Murphy, K. M., & Stockinger, B. (2010) · Nature Immunology · doi:10.1038/ni.1899 · Cited by 482 · see citing works
The Th17 pathway and inflammatory diseases of the intestines, lungs, and skin
Weaver, C. T., Elson, C. O., Fouser, L. A., & Kolls, J. K. (2013) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130318 · Cited by 462 · see citing works
Self-citation
Host–Bacterial Symbiosis in Health and Disease
Chow, J., Lee, S. M., Shen, Y. L., Khosravi, A., & Mazmanian, S. K. (2010) · Advances in immunology · doi:10.1016/b978-0-12-381300-8.00008-3 · Cited by 467 · see citing works
The experimental autoimmune encephalomyelitis (EAE) model of MS
(2014) · Handbook of Clinical Neurology · doi:10.1016/b978-0-444-52001-2.00008-x · Cited by 464 · see citing works
Th22 Cells Are an Important Source of IL-22 for Host Protection against Enteropathogenic Bacteria
Basu, R., O’Quinn, D. B., Silberger, D. J., Schoeb, T. R., Fouser, L. A., Ouyang, W., Hatton, R. D., & Weaver, C. T. (2012) · Immunity · doi:10.1016/j.immuni.2012.08.024 · Cited by 445 · see citing works
Self-citation
Th17 plasticity in human autoimmune arthritis is driven by the inflammatory environment
Nistala, K., Adams, S., Cambrook, H., Ursu, S., Olivito, B., de Jager, W., Evans, J. G., Cimaz, R., Bajaj-Elliott, M., & Wedderburn, L. R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1003852107 · Cited by 443 · see citing works
The PDL1-PD1 Axis Converts Human T H 1 Cells into Regulatory T Cells
Amarnath, S., Mangus, C. W., Wang, J. C. M., Wei, F., He, A., Kapoor, V., Foley, J., Massey, P. R., Felizardo, T. C., Riley, J. L., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3003130 · Cited by 449 · see citing works
The IL-23-IL-17 axis in inflammatory arthritis
Lubberts, E. (2015) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2015.53 · Cited by 442 · see citing works
Modulation of cytokine receptors by IL-2 broadly regulates differentiation into helper T cell lineages
Liao, W., Lin, J.-X., Wang, L., Li, P., & Leonard, W. J. (2011) · Nature Immunology · doi:10.1038/ni.2030 · Cited by 474 · see citing works
Th17 cells are long lived and retain a stem cell-like molecular signature
Muranski, P., Borman, Z. A., Kerkar, S. P., Klebanoff, C. A., Ji, Y., Sanchez-Perez, L., Sukumar, M., Reger, R. N., Yu, Z., Kern, S. J., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.09.019 · Cited by 443 · see citing works
A novel subset of CD4+ TH2 memory/effector cells that produce inflammatory IL-17 cytokine and promote the exacerbation of chronic allergic asthma
Wang, Y.-H., Voo, K. S., Liu, B., Chen, C.-Y., Uygungil, B., Spoede, W., Bernstein, J. A., Huston, D. P., & Liu, Y.-J. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20101376 · Cited by 431 · see citing works
Th17 cells give rise to Th1 cells that are required for the pathogenesis of colitis
Harbour, S. N., Maynard, C. L., Zindl, C. L., Schoeb, T. R., & Weaver, C. T. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1415675112 · Cited by 427 · see citing works
Self-citation
NLRP3 Plays a Critical Role in the Development of Experimental Autoimmune Encephalomyelitis by Mediating Th1 and Th17 Responses
Gris, D., Ye, Z., Iocca, H. A., Wen, H., Craven, R. R., Gris, P., Huang, M., Schneider, M., Miller, S. D., & Ting, J. P.-Y. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0904145 · Cited by 429 · see citing works
Developmental plasticity of Th17 and Treg cells
Lee, Y. K., Mukasa, R., Hatton, R. D., & Weaver, C. T. (2009) · Current Opinion in Immunology · doi:10.1016/j.coi.2009.05.021 · Cited by 423 · see citing works
Self-citation
Th1 and Th17 cells
Damsker, J. M., Hansen, A. M., & Caspi, R. R. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.05133.x · Cited by 424 · see citing works
Origins of CD4+ effector and central memory T cells
Pepper, M., & Jenkins, M. K. (2011) · Nature Immunology · doi:10.1038/ni.2038 · Cited by 401 · see citing works
Interplay between the TH17 and TReg cell lineages: a (co-)evolutionary perspective
Weaver, C. T., & Hatton, R. D. (2009) · Nature reviews. Immunology · doi:10.1038/nri2660 · Cited by 393 · see citing works
Self-citation
High IFN-γ and low SLPI mark severe asthma in mice and humans
Raundhal, M. R., Morse, C., Khare, A., Oriss, T. B., Milošević, J., Trudeau, J. B., Huff, R., Pilewski, J. M., Holguín, F., Kolls, J. K., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci80911 · Cited by 392 · see citing works
The plasticity of human Treg and Th17 cells and its role in autoimmunity
Kleinewietfeld, M., & Hafler, D. A. (2013) · Seminars in Immunology · doi:10.1016/j.smim.2013.10.009 · Cited by 389 · see citing works
T-bet represses TH17 differentiation by preventing Runx1-mediated activation of the gene encoding RORγt
Lazarevic, V., Chen, X., Shim, J., Hwang, E. S., Jang, E., Bolm, A. N., Oukka, M., Kuchroo, V. K., & Glimcher, L. H. (2010) · Nature Immunology · doi:10.1038/ni.1969 · Cited by 389 · see citing works
Essentials of Th17 cell commitment and plasticity
Muranski, P. J., & Restifo, N. P. (2013) · Blood · doi:10.1182/blood-2012-09-378653 · Cited by 386 · see citing works
CD4 T Helper Cell Subsets and Related Human Immunological Disorders
Zhu, X., & Zhu, J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218011 · Cited by 380 · see citing works
Protumor vs Antitumor Functions of IL-17
Murugaiyan, G., & Saha, B. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901017 · Cited by 369 · see citing works
T Helper Cell Differentiation, Heterogeneity, and PlasticityPreprint
Zhu, J. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a030338 · Cited by 352 · see citing works
Expansion of human NK-22 cells with IL-7, IL-2, and IL-1β reveals intrinsic functional plasticity
Cella, M., Otero, K., & Colonna, M. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1005641107 · Cited by 348 · see citing works
TH17 Cells in Asthma and COPD
Alcorn, J. F., Crowe, C. R., & Kolls, J. K. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135926 · Cited by 348 · see citing works
IL-9 as a mediator of Th17-driven inflammatory disease
Nowak, E. C., Weaver, C. T., Turner, H., Begum-Haque, S., Becher, B., Schreiner, B., Coyle, A. J., Kasper, L. H., & Noelle, R. J. (2009) · Journal of Experimental Medicine · doi:10.1084/jem.20090246 · Cited by 393 · see citing works
Self-citation
Transcriptional and Epigenetic Control of T Helper Cell Specification: Molecular Mechanisms Underlying Commitment and Plasticity
Kanno, Y., Vahedi, G., Hirahara, K., Singleton, K., & O'Shea, J. J. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075058 · Cited by 342 · see citing works
Th17 Cells in Cancer: The Ultimate Identity Crisis
Bailey, S. R., Nelson, M. H., Himes, R. A., Li, Z., Mehrotra, S., & Paulos, C. M. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00276 · Cited by 334 · see citing works
Role of Th17 Cells in the Pathogenesis of Human IBD
Gálvez, J. (2014) · ISRN Inflammation · doi:10.1155/2014/928461 · Cited by 317 · see citing works
IL-17 as a future therapeutic target for rheumatoid arthritis
van den Berg, W. B., & Miossec, P. (2009) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2009.179 · Cited by 318 · see citing works
Increased frequency of dual-positive TH2/TH17 cells in bronchoalveolar lavage fluid characterizes a population of patients with severe asthma
Irvin, C., Zafar, I., Good, J. T., Rollins, D. R., Christianson, C. A., Gorska, M. M., Martin, R. J., & Alam, R. (2014) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2014.05.038 · Cited by 318 · see citing works
Helper T cell diversity and plasticity
Nakayamada, S., Takahashi, H., Kanno, Y., & O’Shea, J. J. (2012) · Current Opinion in Immunology · doi:10.1016/j.coi.2012.01.014 · Cited by 317 · see citing works
Systemic and Local Interleukin-17 and Linked Cytokines Associated with Sjögren’s Syndrome Immunopathogenesis
Katsifis, G. E., Rekka, S., Moutsopoulos, N. M., Pillemer, S. R., & Wahl, S. M. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.090319 · Cited by 311 · see citing works
Interleukin-22-Producing Natural Killer Cells and Lymphoid Tissue Inducer-like Cells in Mucosal Immunity
Colonna, M. (2009) · Immunity · doi:10.1016/j.immuni.2009.06.008 · Cited by 305 · see citing works
In vitro–differentiated TH17 cells mediate lethal acute graft-versus-host disease with severe cutaneous and pulmonary pathologic manifestations
Carlson, M., West, M. L., Coghill, J. M., Panoskaltsis‐Mortari, A., Blazar, B. R., & Serody, J. S. (2008) · Blood · doi:10.1182/blood-2008-06-162420 · Cited by 303 · see citing works
Identification of a novel subset of human circulating memory CD4+ T cells that produce both IL-17A and IL-4
Cosmi, L., Maggi, L., Santarlasci, V., Capone, M., Cardilicchia, E., Frosali, F., Querci, V., Angeli, R., Matucci, A., Fambrini, M., et al. (2010) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.10.012 · Cited by 301 · see citing works
Tumor microenvironments direct the recruitment and expansion of human Th17 cells
Su, X., Ye, J., Hsueh, E. C., Zhang, Y., Hoft, D. F., & Peng, G. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0902813 · Cited by 324 · see citing works
IL-17 Immunity in Human Type 1 Diabetes
Honkanen, J. K., Nieminen, J. K., Gao, R., Luopajärvi, K., Salo, H. M., Ilonen, J., Knip, M., Otonkoski, T., & Vaarala, O. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1000788 · Cited by 297 · see citing works
Human T H 17 Cells Are Long-Lived Effector Memory Cells
Kryczek, I., Zhao, E., Liu, Y., Wang, Y., Vatan, L., Szeliga, W., Moyer, J., Klimczak, A., Lange, A., & Zou, W. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002949 · Cited by 278 · see citing works
Interleukin-17 Is Required for T Helper 1 Cell Immunity and Host Resistance to the Intracellular Pathogen Francisella tularensis
Lin, Y., Ritchea, S., Logar, A., Slight-Webb, S. R., Messmer, M. N., Rangel‐Moreno, J., Guglani, L., Alcorn, J. F., Strawbridge, H., Park, S. M., et al. (2009) · Immunity · doi:10.1016/j.immuni.2009.08.025 · Cited by 289 · see citing works
TH17 cell heterogeneity and its role in tissue inflammation
Schnell, A., Littman, D. R., & Kuchroo, V. K. (2023) · Nature Immunology · doi:10.1038/s41590-022-01387-9 · Cited by 286 · see citing works
IL-10 Deficiency Unleashes an Influenza-Specific Th17 Response and Enhances Survival against High-Dose Challenge
McKinstry, K. K., Strutt, T. M., Buck, A. L., Curtis, J. D., Dibble, J. P., Huston, G. E., Tighe, M. P., Hamada, H., Sell, S., Dutton, R. W., et al. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0900657 · Cited by 287 · see citing works
The functional plasticity of T cell subsets
Bluestone, J. A., Mackay, C. R., O’Shea, J. J., & Stockinger, B. (2009) · Nature reviews. Immunology · doi:10.1038/nri2654 · Cited by 286 · see citing works
A cellular and molecular view of T helper 17 cell plasticity in autoimmunity
Stadhouders, R., Lubberts, E., & Hendriks, R. W. (2017) · Journal of Autoimmunity · doi:10.1016/j.jaut.2017.12.007 · Cited by 289 · see citing works
Recent advances in the IL-17 cytokine family
Gaffen, S. L. (2011) · Current Opinion in Immunology · doi:10.1016/j.coi.2011.07.006 · Cited by 283 · see citing works
Effector and Regulatory T-cell Subsets in Autoimmunity and Tissue Inflammation
Jäger, A., & Kuchroo, V. K. (2010) · Scandinavian Journal of Immunology · doi:10.1111/j.1365-3083.2010.02432.x · Cited by 281 · see citing works
T-bet is essential for encephalitogenicity of both Th1 and Th17 cells
Yang, Y.-H., Weiner, J., Liu, Y., Smith, A., Huss, D., Winger, R., Peng, H.-Y., Cravens, P., Racke, M., & Lovett-Racke, A. (2009) · Journal of Experimental Medicine · doi:10.1084/jem.20082584 · Cited by 332 · see citing works
TGF-β and retinoic acid induce the microRNA miR-10a, which targets Bcl-6 and constrains the plasticity of helper T cells
Takahashi, H., Kanno, T., Nakayamada, S., Hirahara, K., Sciumè, G., Muljo, S. A., Kuchen, S., Casellas, R. C., Wei, L., Kanno, Y., et al. (2012) · Nature Immunology · doi:10.1038/ni.2286 · Cited by 281 · see citing works
γδ T Cells Enhance Autoimmunity by Restraining Regulatory T Cell Responses via an Interleukin-23-Dependent Mechanism
Petermann, F., Rothhammer, V., Claussen, M. C., Haas, J. D., Riol‐Blanco, L., Heink, S., Prinz, I., Hemmer, B., Kuchroo, V. K., Oukka, M., et al. (2010) · Immunity · doi:10.1016/j.immuni.2010.08.013 · Cited by 273 · see citing works
Epigenetic Instability of Cytokine and Transcription Factor Gene Loci Underlies Plasticity of the T Helper 17 Cell Lineage
Mukasa, R., Balasubramani, A., Lee, Y. K., Whitley, S. K., Weaver, B. T., Shibata, Y., Crawford, G. E., Hatton, R. D., & Weaver, C. T. (2010) · Immunity · doi:10.1016/j.immuni.2010.04.016 · Cited by 270 · see citing works
Self-citation
Th17 plasticity and its relevance to inflammatory bowel disease
Ueno, A., Jeffery, L. E., Kobayashi, T., Hibi∥, T., Ghosh, S. K., & Jijon, H. B. (2017) · Journal of Autoimmunity · doi:10.1016/j.jaut.2017.12.004 · Cited by 263 · see citing works
IL-22 defines a novel immune pathway of antifungal resistance
De Luca, A., Zelante, T., D'Angelo, C., Zagarella, S., Fallarino, F., Spreca, A., Iannitti, R. G., Bonifazi, P., Renauld, J.-C., Bistoni, F., et al. (2010) · Mucosal Immunology · doi:10.1038/mi.2010.22 · Cited by 265 · see citing works
Development and function of TH17 cells in health and disease
Louten, J., Boniface, K., & Malefyt, R. D. W. (2009) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.04.003 · Cited by 261 · see citing works

T-bet and Runx transcription factors are required for the ontogeny of pathogenic IFNγ-producing Th17 cells (LYM3P.729)
Lazarevic, V., Wang, Y., Godec, J., Ben-Aissa, K., Cui, K., Zhao, K., Pucsek, A. B., Weaver, C. T., & Yagi, R. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.192.supp.64.3
Self-citation
Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages
Harrington, L. E., Hatton, R. D., Mangan, P. R., Turner, H., Murphy, T. L., Murphy, K. M., & Weaver, C. T. (2005) · Nature Immunology · doi:10.1038/ni1254 · Cited by 4,742 · see citing works
Self-citation
The Transcription Factors T-bet and Runx Are Required for the Ontogeny of Pathogenic Interferon-γ-Producing T Helper 17 Cells
Wang, Y., Godec, J., Ben-Aissa, K., Cui, K., Zhao, K., Pucsek, A. B., Lee, Y. K., Weaver, C. T., Yagi, R., & Lazarevic, V. (2014) · Immunity · doi:10.1016/j.immuni.2014.01.002 · Cited by 206 · see citing works
Self-citation
Generation of pathogenic TH17 cells in the absence of TGF-β signalling
Ghoreschi, K., Laurence, A., Yang, X.-P., Tato, C. M., McGeachy, M. J., Konkel, J. E., Ramos, H. L., Wei, L., Davidson, T. S., Bouladoux, N., et al. (2010) · Nature · doi:10.1038/nature09447 · Cited by 1,388 · see citing works
Transforming growth factor β is dispensable for the molecular orchestration of Th17 cell differentiation
Das, J., Ren, G., Zhang, L., Roberts, A. I., Zhao, X., Bothwell, A. L. M., Kaer, L. V., Shi, Y., & Das, G. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20082286 · Cited by 217 · see citing works

Authors: Lee, Y. K., Turner, H., Maynard, C. L., Oliver, J. R., Chen, D., Elson, C. O., & Weaver, C. T.
Affiliations: University of Alabama at Birmingham (US)
Corresponding author: Weaver, Casey T.
ORCID: Lee, Yun Kyung
Maynard, Craig L.
Chen, Dongquan
Elson, Charles O.
Weaver, Casey T.
Venue: Immunity
Publisher: Elsevier BV
Published: 2009-01
Volume: 30
Issue: 1
Pages: 92-107
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2008.11.005
PMC: PMC3607320
OpenAlex: W2011882192
Cited by: 1,053
References: 62
Citations by year: 2026: 19 · 2025: 23 · 2024: 18 · 2023: 32 · 2022: 47 · 2021: 42 · 2020: 47 · 2019: 46 · 2018: 35 · 2017: 56 · 2016: 48 · 2015: 82 · 2014: 81 · 2013: 85 · 2012: 90
FWCI: 56.09
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1694 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Immunity (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
Comprehensive Cancer Center, University of Alabama at Birmingham
National Institute of Allergy and Infectious Diseases (R01AI077574, R01AI035783)
National Institute of Diabetes and Digestive and Kidney Diseases (R24DK064400, P01DK071176)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords: Th17 cells, T helper cell differentiation, developmental plasticity, TGF-beta, interleukin-6, IL-17F, IL-17A, interferon-gamma, STAT4, T-bet, IL-23, IL-12, autoimmunity, Th1 cells
MeSH terms: Animals, Cells, Cultured, Flow Cytometry, Interferon-gamma, T-Lymphocyte Subsets, Transforming Growth Factor beta, Mice, Knockout, Th1 Cells, Th2 Cells, Cell Lineage, Interleukin-17, Mice, Interleukin-23

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

Late Developmental Plasticity in the T Helper 17 Lineage

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks