Bach, J. F. The effect of infections on susceptibility to autoimmune and allergic diseases. N. Engl. J. Med. 347, 911–920 (2002).
Google Scholar
Victora, G. D. & Nussenzweig, M. C. Germinal centers. Annu Rev. Immunol. 40, 413–442 (2022).
Google Scholar
Crotty, S. T follicular helper cell biology: a decade of discovery and diseases. Immunity 50, 1132–1148 (2019).
Google Scholar
Ueno, H., Banchereau, J. & Vinuesa, C. G. Pathophysiology of T follicular helper cells in humans and mice. Nat. Immunol. 16, 142–152 (2015).
Google Scholar
Seth, A. & Craft, J. Spatial and functional heterogeneity of follicular helper T cells in autoimmunity. Curr. Opin. Immunol. 61, 1–9 (2019).
Google Scholar
Victora, G. D. et al. Germinal center dynamics revealed by multiphoton microscopy with a photoactivatable fluorescent reporter. Cell 143, 592–605 (2010).
Google Scholar
Lee, S. E., Rudd, B. D. & Smith, N. L. Fate-mapping mice: new tools and technology for immune discovery. Trends Immunol. 43, 195–209 (2022).
Google Scholar
Jacobsen, J. T. et al. Expression of Foxp3 by T follicular helper cells in end-stage germinal centers. Science 373, eabe5146 (2021).
Google Scholar
Al Khabouri, S. & Gerlach, C. T cell fate mapping and lineage tracing technologies probing clonal aspects underlying the generation of CD8 T cell subsets. Scand. J. Immunol. 92, e12983 (2020).
Google Scholar
Fang, D. et al. Transient T-bet expression functionally specifies a distinct T follicular helper subset. J. Exp. Med. 215, 2705–2714 (2018).
Google Scholar
Hirota, K. et al. Plasticity of Th17 cells in Peyer’s patches is responsible for the induction of T cell-dependent IgA responses. Nat. Immunol. 14, 372–379 (2013).
Google Scholar
Ruff, W. E., Greiling, T. M. & Kriegel, M. A. Host-microbiota interactions in immune-mediated diseases. Nat. Rev. Microbiol. 18, 521–538 (2020).
Google Scholar
Wu, H. J. et al. Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 32, 815–827 (2010).
Google Scholar
Teng, F. et al. Gut microbiota drive autoimmune arthritis by promoting differentiation and migration of Peyer’s patch T follicular helper cells. Immunity 44, 875–888 (2016).
Google Scholar
Huang, H., Benoist, C. & Mathis, D. Rituximab specifically depletes short-lived autoreactive plasma cells in a mouse model of inflammatory arthritis. Proc. Natl Acad. Sci. USA 107, 4658–4663 (2010).
Google Scholar
Lee, J. Y. et al. The transcription factor KLF2 restrains CD4+ T follicular helper cell differentiation. Immunity 42, 252–264 (2015).
Google Scholar
Mora, J. R. et al. Selective imprinting of gut-homing T cells by Peyer’s patch dendritic cells. Nature 424, 88–93 (2003).
Google Scholar
Iwata, M. et al. Retinoic acid imprints gut-homing specificity on T cells. Immunity 21, 527–538 (2004).
Google Scholar
Ansaldo, E. et al. Akkermansia muciniphila induces intestinal adaptive immune responses during homeostasis. Science 364, 1179–1184 (2019).
Google Scholar
Andersson, A. et al. Estrogen regulates T helper 17 phenotype and localization in experimental autoimmune arthritis. Arthritis Res Ther. 17, 32 (2015).
Google Scholar
Mullershausen, F. et al. Persistent signaling induced by FTY720-phosphate is mediated by internalized S1P1 receptors. Nat. Chem. Biol. 5, 428–434 (2009).
Google Scholar
Baeyens, A., Fang, V., Chen, C. & Schwab, S. R. Exit strategies: S1P signaling and T cell migration. Trends Immunol. 36, 778–787 (2015).
Google Scholar
Yang, Y. et al. Focused specificity of intestinal TH17 cells towards commensal bacterial antigens. Nature 510, 152–156 (2014).
Google Scholar
Bradley, C. P. et al. Segmented filamentous bacteria provoke lung autoimmunity by inducing gut-lung axis Th17 cells expressing dual TCRs. Cell Host Microbe 22, 697–704 (2017).
Google Scholar
Ivanov, I. I. et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139, 485–498 (2009).
Google Scholar
LaBranche, T. P. et al. Characterization of the KRN cell transfer model of rheumatoid arthritis (KRN-CTM), a chronic yet synchronized version of the K/BxN mouse. Am. J. Pathol. 177, 1388–1396 (2010).
Google Scholar
Hall, J. A. et al. Transcription factor RORα enforces stability of the Th17 cell effector program by binding to a Rorc cis-regulatory element. Immunity 55, 2027–2043 (2022).
Google Scholar
Ivanov, I. I. et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126, 1121–1133 (2006).
Google Scholar
Vacchio, M. S. et al. A Thpok-directed transcriptional circuitry promotes Bcl6 and Maf expression to orchestrate T follicular helper differentiation. Immunity 51, 465–478 (2019).
Google Scholar
Kroenke, M. A. et al. Bcl6 and Maf cooperate to instruct human follicular helper CD4 T cell differentiation. J. Immunol. 188, 3734–3744 (2012).
Google Scholar
Reinhardt, R. L., Liang, H. E. & Locksley, R. M. Cytokine-secreting follicular T cells shape the antibody repertoire. Nat. Immunol. 10, 385–393 (2009).
Google Scholar
Yeh, C. H., Finney, J., Okada, T., Kurosaki, T. & Kelsoe, G. Primary germinal center-resident T follicular helper cells are a physiologically distinct subset of CXCR5hiPD-1hi T follicular helper cells. Immunity 55, 272–289.e277 (2022).
Google Scholar
Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005).
Google Scholar
Crotty, S. Follicular helper CD4 T cells (TFH). Annu Rev. Immunol. 29, 621–663 (2011).
Google Scholar
Zotos, D. et al. IL-21 regulates germinal center B cell differentiation and proliferation through a B cell-intrinsic mechanism. J. Exp. Med. 207, 365–378 (2010).
Google Scholar
Linterman, M. A. et al. IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses. J. Exp. Med. 207, 353–363 (2010).
Google Scholar
Misiak, J., Tarte, K. & Amé-Thomas, P. in T Follicular Helper Cells: Methods and Protocols (eds Espéli, M. & Linterman, M.) 163–173 (Springer, 2015).
Bauquet, A. T. et al. The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells. Nat. Immunol. 10, 167–175 (2009).
Google Scholar
Wu, X. et al. Single-cell sequencing of immune cells from anticitrullinated peptide antibody positive and negative rheumatoid arthritis. Nat. Commun. 12, 4977 (2021).
Google Scholar
Yang, X. O. et al. T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity 28, 29–39 (2008).
Google Scholar
Gaffen, S. L., Jain, R., Garg, A. V. & Cua, D. J. The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing. Nat. Rev. Immunol. 14, 585–600 (2014).
Google Scholar
Lavelle, E. C. & Ward, R. W. Mucosal vaccines: fortifying the frontiers. Nat. Rev. Immunol. 22, 236–250 (2022).
Google Scholar
Allen, C. D. et al. Germinal center dark and light zone organization is mediated by CXCR4 and CXCR5. Nat. Immunol. 5, 943–952 (2004).
Google Scholar
Cinamon, G. et al. Sphingosine 1-phosphate receptor 1 promotes B cell localization in the splenic marginal zone. Nat. Immunol. 5, 713–720 (2004).
Google Scholar
Vinuesa, C. G., Linterman, M. A., Yu, D. & MacLennan, I. C. Follicular helper T cells. Annu. Rev. Immunol. 34, 335–368 (2016).
Google Scholar
Silva-Cayetano, A. et al. Spatial dysregulation of T follicular helper cells impairs vaccine responses in aging. Nat. Immunol. 24, 1124–1137 (2023).
Google Scholar
Goronzy, J. J. & Weyand, C. M. Immune aging and autoimmunity. Cell. Mol. Life Sci. 69, 1615–1623 (2012).
Google Scholar
Volkov, M., van Schie, K. A. & van der Woude, D. Autoantibodies and B cells: the ABC of rheumatoid arthritis pathophysiology. Immunol. Rev. 294, 148–163 (2020).
Google Scholar
Vergroesen, R. D. et al. B-cell receptor sequencing of anti-citrullinated protein antibody (ACPA) IgG-expressing B cells indicates a selective advantage for the introduction of N-glycosylation sites during somatic hypermutation. Ann. Rheum. Dis. 77, 956–958 (2018).
Google Scholar
Chang, Y. et al. TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf. Sci. Immunol. 9, eadd4818 (2024).
Google Scholar
Gabrysova, L. et al. c-Maf controls immune responses by regulating disease-specific gene networks and repressing IL-2 in CD4+ T cells. Nat. Immunol. 19, 497–507 (2018).
Google Scholar
Brockmann, L. et al. Intestinal microbiota-specific Th17 cells possess regulatory properties and suppress effector T cells via c-MAF and IL-10. Immunity 56, 2719–2735 (2023).
Google Scholar
Heath, W. R. et al. Expression of two T cell receptor alpha chains on the surface of normal murine T cells. Eur. J. Immunol. 25, 1617–1623 (1995).
Google Scholar
Padovan, E. et al. Expression of two T cell receptor alpha chains: dual receptor T cells. Science 262, 422–424 (1993).
Google Scholar
Tlustochowicz, W. et al. Efficacy and safety of subcutaneous and intravenous loading dose regimens of secukinumab in patients with active rheumatoid arthritis: results from a randomized phase II study. J. Rheumatol. 43, 495–503 (2016).
Google Scholar
Genovese, M. C. et al. Efficacy and safety of secukinumab in patients with rheumatoid arthritis: a phase II, dose-finding, double-blind, randomised, placebo controlled study. Ann. Rheum. Dis. 72, 863–869 (2013).
Google Scholar
Dahdal, S. et al. Residual activatability of circulating Tfh17 predicts humoral response to thymodependent antigens in patients on therapeutic immunosuppression. Front. Immunol. 9, 3178 (2018).
Google Scholar
Gao, X. et al. T follicular helper 17 (Tfh17) cells are superior for immunological memory maintenance. eLife 12, e82217 (2023).
Google Scholar
Xu, M. et al. c-MAF-dependent regulatory T cells mediate immunological tolerance to a gut pathobiont. Nature 554, 373–377 (2018).
Google Scholar
Dixit, D. et al. S1PR1 inhibition induces proapoptotic signaling in T cells and limits humoral responses within lymph nodes. J. Clin. Invest. 134, e174984 (2024).
Google Scholar
Badr, M. E., Zhang, Z., Tai, X. & Singer, A. CD8 T cell tolerance results from eviction of immature autoreactive cells from the thymus. Science 382, 534–541 (2023).
Google Scholar
Dauner, J. G., Chappell, C. P., Williams, I. R. & Jacob, J. Perfusion fixation preserves enhanced yellow fluorescent protein and other cellular markers in lymphoid tissues. J. Immunol. Methods 340, 116–122 (2009).
Google Scholar
Kim, S. T. et al. Human extrafollicular CD4+ Th cells help memory B cells produce Igs. J. Immunol. 201, 1359–1372 (2018).
Google Scholar
Ise, W. et al. T follicular helper cell-germinal center B cell interaction strength regulates entry into plasma cell or recycling germinal center cell fate. Immunity 48, 702–715 (2018).
Google Scholar
Sage, P. T., Paterson, A. M., Lovitch, S. B. & Sharpe, A. H. The coinhibitory receptor CTLA-4 controls B cell responses by modulating T follicular helper, T follicular regulatory, and T regulatory cells. Immunity 41, 1026–1039 (2014).
Google Scholar
Ahmed, R. et al. Human stem cell-like memory T cells are maintained in a state of dynamic flux. Cell Rep. 17, 2811–2818 (2016).
Google Scholar
Gattinoni, L. et al. A human memory T cell subset with stem cell-like properties. Nat. Med. 17, 1290–1297 (2011).
Google Scholar
Merico, D., Isserlin, R., Stueker, O., Emili, A. & Bader, G. D. Enrichment map: a network-based method for gene-set enrichment visualization and interpretation. PLoS ONE 5, e13984 (2010).
Google Scholar
