Abstract
The gastrointestinal tract is colonized with a huge number of microbes, which are instrumental for the development, homeostasis, and fine-tuning of the immune system. Recent evidence suggests that microbiota very efficiently modulates conventional and regulatory T cell responses that are required for effective host defense against invading pathogens and avoidance of autoimmunity and other immunopathologic conditions, respectively. In this review, we discuss the interplay between the microbiota and T cells, with a particular focus on the de novo induction of regulatory T cells within gut-draining lymph nodes (LNs), the impact of microbiota-derived metabolites on T cell differentiation, and the functional role of unique regulatory T cell subsets within the intestinal immune system.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abbas, A. K., Murphy, K. M., & Sher, A. (1996). Functional diversity of helper T lymphocytes. Nature, 383, 787–793.
Abe, J., Shichino, S., Ueha, S., Hashimoto, S., Tomura, M., Inagaki, Y., Stein, J. V., & Matsushima, K. (2014). Lymph node stromal cells negatively regulate antigen-specific CD4+ T cell responses. Journal of Immunology, 193, 1636–1644.
Acton, S. E., Farrugia, A. J., Astarita, J. L., Mourao-Sa, D., Jenkins, R. P., Nye, E., Hooper, S., van Blijswijk, J., Rogers, N. C., Snelgrove, K. J., et al. (2014). Dendritic cells control fibroblastic reticular network tension and lymph node expansion. Nature, 514, 498–502.
Agace, W. W. (2006). Tissue-tropic effector T cells: Generation and targeting opportunities. Nature Reviews Immunology, 6, 682–692.
Ahrendt, M., Hammerschmidt, S. I., Pabst, O., Pabst, R., & Bode, U. (2008). Stromal cells confer lymph node-specific properties by shaping a unique microenvironment influencing local immune responses. Journal of Immunology, 181, 1898–1907.
Allen, J. E., & Maizels, R. M. (2011). Diversity and dialogue in immunity to helminths. Nature Reviews Immunology, 11, 375–388.
Amsen, D., Spilianakis, C. G., & Flavell, R. A. (2009). How are T(H)1 and T(H)2 effector cells made? Current Opinion in Immunology, 21, 153–160.
Arpaia, N., Campbell, C., Fan, X., Dikiy, S., van der Veeken, J., deRoos, P., Liu, H., Cross, J. R., Pfeffer, K., Coffer, P. J., & Rudensky, A. Y. (2013). Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature, 504, 451–455.
Atarashi, K., Tanoue, T., Shima, T., Imaoka, A., Kuwahara, T., Momose, Y., Cheng, G., Yamasaki, S., Saito, T., Ohba, Y., et al. (2011). Induction of colonic regulatory T cells by indigenous Clostridium species. Science, 331, 337–341.
Atarashi, K., Tanoue, T., Oshima, K., Suda, W., Nagano, Y., Nishikawa, H., Fukuda, S., Saito, T., Narushima, S., Hase, K., et al. (2013). Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature, 500, 232–236.
Bach, J. F. (2003). Regulatory T cells under scrutiny. Nature Reviews Immunology, 3, 189–198.
Bain, C. C., & Mowat, A. M. (2014). Macrophages in intestinal homeostasis and inflammation. Immunological Reviews, 260, 102–117.
Bajenoff, M. (2012). Stromal cells control soluble material and cellular transport in lymph nodes. Frontiers in Immunology, 3, 304.
Banchereau, J., Pascual, V., & O’Garra, A. (2012). From IL-2 to IL-37: The expanding spectrum of anti-inflammatory cytokines. Nature Immunology, 13, 925–931.
Baptista, A. P., Roozendaal, R., Reijmers, R. M., Koning, J. J., Unger, W. W., Greuter, M., Keuning, E. D., Molenaar, R., Goverse, G., Sneeboer, M. M., et al. (2014). Lymph node stromal cells constrain immunity via MHC class II self-antigen presentation. eLife, 3, e04433.
Barthels, C., Ogrinc, A., Steyer, V., Meier, S., Simon, F., Wimmer, M., Blutke, A., Straub, T., Zimber-Strobl, U., Lutgens, E., et al. (2017). CD40-signalling abrogates induction of RORγt+ Treg cells by intestinal CD103+ DCs and causes fatal colitis. Nature Communications, 8, 14715.
Belkaid, Y., & Hand, T. W. (2014). Role of the microbiota in immunity and inflammation. Cell, 157, 121–141.
Benson, M. J., Pino-Lagos, K., Rosemblatt, M., & Noelle, R. J. (2007). All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation. The Journal of Experimental Medicine, 204, 1765–1774.
Blander, J. M., Torchinsky, M. B., & Campisi, L. (2012). Revisiting the old link between infection and autoimmune disease with commensals and T helper 17 cells. Immunologic Research, 54, 50–68.
Bopp, T., Becker, C., Klein, M., Klein-Hessling, S., Palmetshofer, A., Serfling, E., Heib, V., Becker, M., Kubach, J., Schmitt, S., et al. (2007). Cyclic adenosine monophosphate is a key component of regulatory T cell-mediated suppression. The Journal of Experimental Medicine, 204, 1303–1310.
Breese, E., Braegger, C. P., Corrigan, C. J., Walker-Smith, J. A., & Macdonald, T. T. (1993). Interleukin-2- and interferon-γ-secreting T cells in normal and diseased human intestinal mucosa. Immunology, 78, 5.
Cao, X., Cai, S. F., Fehniger, T. A., Song, J., Collins, L. I., Piwnica-Worms, D. R., & Ley, T. J. (2007). Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. Immunity, 27, 635–646.
Cebula, A., Seweryn, M., Rempala, G. A., Pabla, S. S., McIndoe, R. A., Denning, T. L., Bry, L., Kraj, P., Kisielow, P., & Ignatowicz, L. (2013). Thymus-derived regulatory T cells contribute to tolerance to commensal microbiota. Nature, 497, 258–262.
Cerovic, V., Houston, S. A., Scott, C. L., Aumeunier, A., Yrlid, U., Mowat, A. M., & Milling, S. W. (2013). Intestinal CD103− dendritic cells migrate in lymph and prime effector T cells. Mucosal Immunology, 6, 104–113.
Cerovic, V., Bain, C. C., Mowat, A. M., & Milling, S. W. (2014). Intestinal macrophages and dendritic cells: What’s the difference? Trends in Immunology, 35, 270–277.
Chellappa, S., Hugenschmidt, H., Hagness, M., Line, P. D., Labori, K. J., Wiedswang, G., Tasken, K., & Aandahl, E. M. (2016). Regulatory T cells that co-express RORγt and FOXP3 are pro-inflammatory and immunosuppressive and expand in human pancreatic cancer. Oncoimmunology, 5, e1102828.
Ciofani, M., & Zuniga-Pflucker, J. C. (2010). Determining gd versus ab T cell development. Nature Reviews Immunology, 10, 657–663.
Coombes, J. L., Siddiqui, K. R., Arancibia-Carcamo, C. V., Hall, J., Sun, C. M., Belkaid, Y., & Powrie, F. (2007). A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGFb and retinoic acid-dependent mechanism. The Journal of Experimental Medicine, 204, 1757–1764.
Coquet, J. M., Middendorp, S., van der Horst, G., Kind, J., Veraar, E. A., Xiao, Y., Jacobs, H., & Borst, J. (2013). The CD27 and CD70 costimulatory pathway inhibits effector function of T helper 17 cells and attenuates associated autoimmunity. Immunity, 38, 53–65.
Cording, S., Wahl, B., Kulkarni, D., Chopra, H., Pezoldt, J., Buettner, M., Dummer, A., Hadis, U., Heimesaat, M., Bereswill, S., et al. (2014). The intestinal micro-environment imprints stromal cells to promote efficient Treg induction in gut-draining lymph nodes. Mucosal Immunology, 7, 359–368.
Cretney, E., Kallies, A., & Nutt, S. L. (2013). Differentiation and function of Foxp3+ effector regulatory T cells. Trends in Immunology, 34, 74–80.
Crohn, B. B., Ginzburg, L., & Oppenheimer, G. D. (1932). Regional ileitis: A pathologic and clinical entity. Journal of the American Medical Association, 99, 1323–1329.
Cui, G., Zhang, Y., Gong, Z., Zhang, J. Z., & Zang, Y. Q. (2009). Induction of CD4+CD25+Foxp3+ regulatory T cell response by glatiramer acetate in type 1 diabetes. Cell Research, 19, 574–583.
Dambacher, J., Beigel, F., Zitzmann, K., De Toni, E. N., Goke, B., Diepolder, H. M., Auernhammer, C. J., & Brand, S. (2009). The role of the novel Th17 cytokine IL-26 in intestinal inflammation. Gut, 58, 1207–1217.
Darrasse-Jeze, G., Deroubaix, S., Mouquet, H., Victora, G. D., Eisenreich, T., Yao, K. H., Masilamani, R. F., Dustin, M. L., Rudensky, A., Liu, K., & Nussenzweig, M. C. (2009). Feedback control of regulatory T cell homeostasis by dendritic cells in vivo. The Journal of Experimental Medicine, 206, 1853–1862.
Delacher, M., Imbusch, C. D., Weichenhan, D., Breiling, A., Hotz-Wagenblatt, A., Trager, U., Hofer, A. C., Kagebein, D., Wang, Q., Frauhammer, F., et al. (2017). Genome-wide DNA-methylation landscape defines specialization of regulatory T cells in tissues. Nature Immunology, 18(10), 1160–1172.
Dubrot, J., Duraes, F. V., Potin, L., Capotosti, F., Brighouse, D., Suter, T., LeibundGut-Landmann, S., Garbi, N., Reith, W., Swartz, M. A., & Hugues, S. (2014). Lymph node stromal cells acquire peptide-MHCII complexes from dendritic cells and induce antigen-specific CD4+ T cell tolerance. The Journal of Experimental Medicine, 211, 1153–1166.
Dudda, J. C., Lembo, A., Bachtanian, E., Huehn, J., Siewert, C., Hamann, A., Kremmer, E., Forster, R., & Martin, S. F. (2005). Dendritic cells govern induction and reprogramming of polarized tissue-selective homing receptor patterns of T cells: Important roles for soluble factors and tissue microenvironments. European Journal of Immunology, 35, 1056–1065.
Dwyer, K. M., Deaglio, S., Gao, W., Friedman, D., Strom, T. B., & Robson, S. C. (2007). CD39 and control of cellular immune responses. Purinergic Signalling, 3, 171–180.
Ebbo, M., Crinier, A., Vely, F., & Vivier, E. (2017). Innate lymphoid cells: Major players in inflammatory diseases. Nature Reviews Immunology, 17(11), 665–678.
Elinav, E., Strowig, T., Kau, A. L., Henao-Mejia, J., Thaiss, C. A., Booth, C. J., Peaper, D. R., Bertin, J., Eisenbarth, S. C., Gordon, J. I., & Flavell, R. A. (2011). NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell, 145, 745–757.
Elson, C. O., Graeff, A. S., James, S. P., & Strober, W. (1981). Covert suppressor T cells in Crohn’s disease. Gastroenterology, 80, 1513–1521.
Eyerich, S., Eyerich, K., Pennino, D., Carbone, T., Nasorri, F., Pallotta, S., Cianfarani, F., Odorisio, T., Traidl-Hoffmann, C., Behrendt, H., et al. (2009). Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling. The Journal of Clinical Investigation, 119, 3573–3585.
Feuerer, M., Hill, J. A., Kretschmer, K., von Boehmer, H., Mathis, D., & Benoist, C. (2010). Genomic definition of multiple ex vivo regulatory T cell subphenotypes. Proceedings of the National Academy of Sciences of the United States of America, 107, 5919–5924.
Fletcher, A. L., Lukacs-Kornek, V., Reynoso, E. D., Pinner, S. E., Bellemare-Pelletier, A., Curry, M. S., Collier, A. R., Boyd, R. L., & Turley, S. J. (2010). Lymph node fibroblastic reticular cells directly present peripheral tissue antigen under steady-state and inflammatory conditions. The Journal of Experimental Medicine, 207, 689–697.
Fletcher, A. L., Acton, S. E., & Knoblich, K. (2015). Lymph node fibroblastic reticular cells in health and disease. Nature Reviews Immunology, 15, 350–361.
Floess, S., Freyer, J., Siewert, C., Baron, U., Olek, S., Polansky, J., Schlawe, K., Chang, H. D., Bopp, T., Schmitt, E., et al. (2007). Epigenetic control of the foxp3 locus in regulatory T cells. PLoS Biology, 5, e38.
Fontenot, J. D., Gavin, M. A., & Rudensky, A. Y. (2003). Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nature Immunology, 4, 330–336.
Franke, A., McGovern, D. P., Barrett, J. C., Wang, K., Radford-Smith, G. L., Ahmad, T., Lees, C. W., Balschun, T., Lee, J., Roberts, R., et al. (2010). Genome-wide meta-analysis increases to 71 the number of confirmed Crohn’s disease susceptibility loci. Nature Genetics, 42, 1118–1125.
Fujimoto, K., Karuppuchamy, T., Takemura, N., Shimohigoshi, M., Machida, T., Haseda, Y., Aoshi, T., Ishii, K. J., Akira, S., & Uematsu, S. (2011). A new subset of CD103+CD8a+ dendritic cells in the small intestine expresses TLR3, TLR7, and TLR9 and induces Th1 response and CTL activity. Journal of Immunology, 186, 6287–6295.
Furusawa, Y., Obata, Y., Fukuda, S., Endo, T. A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., Kato, T., et al. (2013). Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature, 504, 446–450.
Fuss, I. J., Heller, F., Boirivant, M., Leon, F., Yoshida, M., Fichtner-Feigl, S., Yang, Z., Exley, M., Kitani, A., Blumberg, R. S., et al. (2004). Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis. The Journal of Clinical Investigation, 113, 1490–1497.
Gavin, M. A., Rasmussen, J. P., Fontenot, J. D., Vasta, V., Manganiello, V. C., Beavo, J. A., & Rudensky, A. Y. (2007). Foxp3-dependent programme of regulatory T-cell differentiation. Nature, 445, 771–775.
Gerlach, K., Hwang, Y., Nikolaev, A., Atreya, R., Dornhoff, H., Steiner, S., Lehr, H. A., Wirtz, S., Vieth, M., Waisman, A., et al. (2014). TH9 cells that express the transcription factor PU.1 drive T cell-mediated colitis via IL-9 receptor signaling in intestinal epithelial cells. Nature Immunology, 15, 676–686.
Gerner, M. Y., Kastenmuller, W., Ifrim, I., Kabat, J., & Germain, R. N. (2012). Histo-cytometry: A method for highly multiplex quantitative tissue imaging analysis applied to dendritic cell subset microanatomy in lymph nodes. Immunity, 37, 364–376.
Gottschalk, R. A., Corse, E., & Allison, J. P. (2012). Expression of Helios in peripherally induced Foxp3+ regulatory T cells. Journal of Immunology, 188, 976–980.
Gretz, J. E., Norbury, C. C., Anderson, A. O., Proudfoot, A. E., & Shaw, S. (2000). Lymph-borne chemokines and other low molecular weight molecules reach high endothelial venules via specialized conduits while a functional barrier limits access to the lymphocyte microenvironments in lymph node cortex. The Journal of Experimental Medicine, 192, 1425–1440.
Gross, M., Salame, T. M., & Jung, S. (2015). Guardians of the Gut – murine intestinal macrophages and dendritic cells. Frontiers in Immunology, 6, 254.
Guo, X., Qiu, J., Tu, T., Yang, X., Deng, L., Anders, R. A., Zhou, L., & Fu, Y. X. (2014). Induction of innate lymphoid cell-derived interleukin-22 by the transcription factor STAT3 mediates protection against intestinal infection. Immunity, 40, 25–39.
Hadis, U., Wahl, B., Schulz, O., Hardtke-Wolenski, M., Schippers, A., Wagner, N., Muller, W., Sparwasser, T., Forster, R., & Pabst, O. (2011). Intestinal tolerance requires gut homing and expansion of FoxP3+ regulatory T cells in the lamina propria. Immunity, 34, 237–246.
Halim, L., Romano, M., McGregor, R., Correa, I., Pavlidis, P., Grageda, N., Hoong, S. J., Yuksel, M., Jassem, W., Hannen, R. F., et al. (2017). An Atlas of human regulatory T helper-like cells reveals features of Th2-like Tregs that support a tumorigenic environment. Cell Reports, 20, 757–770.
Hall, J. A., Bouladoux, N., Sun, C. M., Wohlfert, E. A., Blank, R. B., Zhu, Q., Grigg, M. E., Berzofsky, J. A., & Belkaid, Y. (2008). Commensal DNA limits regulatory T cell conversion and is a natural adjuvant of intestinal immune responses. Immunity, 29, 637–649.
Halpern, B., Zweibaum, A., Oriol Palau, R., & Monrard, J. C. (1967). Experimental immune ulcerative colitis. In: Miescher, P., & Grabar, P. (Eds.), International symposium (pp. 161–178). Basel.
Hammerschmidt, S. I., Ahrendt, M., Bode, U., Wahl, B., Kremmer, E., Forster, R., & Pabst, O. (2008). Stromal mesenteric lymph node cells are essential for the generation of gut-homing T cells in vivo. The Journal of Experimental Medicine, 205, 2483–2490.
Happel, K. I., Dubin, P. J., Zheng, M., Ghilardi, N., Lockhart, C., Quinton, L. J., Odden, A. R., Shellito, J. E., Bagby, G. J., Nelson, S., & Kolls, J. K. (2005). Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae. The Journal of Experimental Medicine, 202, 761–769.
Haribhai, D., Williams, J. B., Jia, S., Nickerson, D., Schmitt, E. G., Edwards, B., Ziegelbauer, J., Yassai, M., Li, S. H., Relland, L. M., et al. (2011). A requisite role for induced regulatory T cells in tolerance based on expanding antigen receptor diversity. Immunity, 35, 109–122.
He, Z., Ma, J., Wang, R., Zhang, J., Huang, Z., Wang, F., Sen, S., Rothenberg, E. V., & Sun, Z. (2017). A two-amino-acid substitution in the transcription factor RORγt disrupts its function in TH17 differentiation but not in thymocyte development. Nature Immunology, 18(10), 1128–1113.
Heller, F., Florian, P., Bojarski, C., et al. (2005). Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterology, 129, 15.
Hill, J. A., Feuerer, M., Tash, K., Haxhinasto, S., Perez, J., Melamed, R., Mathis, D., & Benoist, C. (2007). Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature. Immunity, 27, 786–800.
Hill, J. A., Hall, J. A., Sun, C. M., Cai, Q., Ghyselinck, N., Chambon, P., Belkaid, Y., Mathis, D., & Benoist, C. (2008). Retinoic acid enhances Foxp3 induction indirectly by relieving inhibition from CD4+CD44hi Cells. Immunity, 29, 758–770.
Hodgson, H. J., Wands, J. R., & Isselbacher, K. J. (1978). Decreased suppressor cell activity in inflammatory bowel disease. Clinical and Experimental Immunology, 32, 451–458.
Hogquist, K. A., Baldwin, T. A., & Jameson, S. C. (2005). Central tolerance: Learning self-control in the thymus. Nature Reviews Immunology, 5, 772–782.
Hori, S., Nomura, T., & Sakaguchi, S. (2003). Control of regulatory T cell development by the transcription factor Foxp3. Science, 299, 1057–1061.
Huehn, J., & Beyer, M. (2015). Epigenetic and transcriptional control of Foxp3 regulatory T cells. Seminars in Immunology, 27, 10–18.
Huehn, J., Polansky, J. K., & Hamann, A. (2009). Epigenetic control of FOXP3 expression: The key to a stable regulatory T-cell lineage? Nature Reviews Immunology, 9, 83–89.
Infante-Duarte, C., Horton, H. F., Byrne, M. C., & Kamradt, T. (2000). Microbial lipopeptides induce the production of IL-17 in Th cells. The Journal of Immunology, 165, 6107–6115.
Ivanov, I. I., Atarashi, K., Manel, N., Brodie, E. L., Shima, T., Karaoz, U., Wei, D., Goldfarb, K. C., Santee, C. A., Lynch, S. V., et al. (2009). Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell, 139, 485–498.
Josefowicz, S. Z., Lu, L. F., & Rudensky, A. Y. (2012a). Regulatory T cells: Mechanisms of differentiation and function. Annual Review of Immunology, 30, 531–564.
Josefowicz, S. Z., Niec, R. E., Kim, H. Y., Treuting, P., Chinen, T., Zheng, Y., Umetsu, D. T., & Rudensky, A. Y. (2012b). Extrathymically generated regulatory T cells control mucosal TH2 inflammation. Nature, 482, 395–399.
Kamada, N., Seo, S. U., Chen, G. Y., & Nunez, G. (2013). Role of the gut microbiota in immunity and inflammatory disease. Nature Reviews Immunology, 13, 321–335.
Kamath, A. T., Henri, S., Battye, F., Tough, D. F., & Shortman, K. (2002). Developmental kinetics and lifespan of dendritic cells in mouse lymphoid organs. Blood, 100, 1734–1741.
Kang, S. G., Lim, H. W., Andrisani, O. M., Broxmeyer, H. E., & Kim, C. H. (2007). Vitamin A metabolites induce gut-homing FoxP3+ regulatory T cells. Journal of Immunology, 179, 3724–3733.
Kaplan, M. H. (2013). Th9 cells: Differentiation and disease. Immunological Reviews, 252, 104–115.
Kaplan, M. H., Hufford, M. M., & Olson, M. R. (2015). The development and in vivo function of T helper 9 cells. Nature Reviews Immunology, 15, 295–307.
Khan, O., Headley, M., Gerard, A., Wei, W., Liu, L., & Krummel, M. F. (2011). Regulation of T cell priming by lymphoid stroma. PLoS One, 6, e26138.
Kim, H. P., & Leonard, W. J. (2007). CREB/ATF-dependent T cell receptor-induced FoxP3 gene expression: A role for DNA methylation. The Journal of Experimental Medicine, 204, 1543–1551.
Kim, M. H., Kang, S. G., Park, J. H., Yanagisawa, M., & Kim, C. H. (2013a). Short-chain fatty acids activate GPR41 and GPR43 on intestinal epithelial cells to promote inflammatory responses in mice. Gastroenterology, 145(396–406), e391–e310.
Kim, S. V., Xiang, W. V., Kwak, C., Yang, Y., Lin, X. W., Ota, M., Sarpel, U., Rifkin, D. B., Xu, R., & Littman, D. R. (2013b). GPR15-mediated homing controls immune homeostasis in the large intestine mucosa. Science, 340(6139), 1456–1459.
Kim, K. S., Hong, S. W., Han, D., Yi, J., Jung, J., Yang, B. G., Lee, J. Y., Lee, M., & Surh, C. D. (2016). Dietary antigens limit mucosal immunity by inducing regulatory T cells in the small intestine. Science, 351(6275), 858–863.
Kinnebrew, M. A., Buffie, C. G., Diehl, G. E., Zenewicz, L. A., Leiner, I., Hohl, T. M., Flavell, R. A., Littman, D. R., & Pamer, E. G. (2012). Interleukin 23 production by intestinal CD103+CD11b+ dendritic cells in response to bacterial flagellin enhances mucosal innate immune defense. Immunity, 36, 276–287.
Klein, L., Hinterberger, M., Wirnsberger, G., & Kyewski, B. (2009). Antigen presentation in the thymus for positive selection and central tolerance induction. Nature Reviews Immunology, 9, 833–844.
Kluger, M. A., Luig, M., Wegscheid, C., Goerke, B., Paust, H. J., Brix, S. R., Yan, I., Mittrucker, H. W., Hagl, B., Renner, E. D., et al. (2014). Stat3 programs Th17-specific regulatory T cells to control GN. Journal of the American Society of Nephrology, 25, 1291–1302.
Kluger, M. A., Meyer, M. C., Nosko, A., Goerke, B., Luig, M., Wegscheid, C., Tiegs, G., Stahl, R. A., Panzer, U., & Steinmetz, O. M. (2016). RORγt+Foxp3+ cells are an independent bifunctional regulatory T cell lineage and mediate crescentic GN. Journal of the American Society of Nephrology, 27, 454–465.
Korn, L. L., Hubbeling, H. G., Porrett, P. M., Yang, Q., Barnett, L. G., & Laufer, T. M. (2014). Regulatory T cells occupy an isolated niche in the intestine that is antigen independent. Cell Reports, 9, 1567–1573.
Kosiewicz, M. M., Zirnheld, A. L., & Alard, P. (2011). Gut microbiota, immunity, and disease: A complex relationship. Frontiers in Microbiology, 2, 180.
Kuhn, K. A., & Stappenbeck, T. S. (2013). Peripheral education of the immune system by the colonic microbiota. Seminars in Immunology, 25, 364–369.
Laouar, A., Haridas, V., Vargas, D., Zhinan, X., Chaplin, D., van Lier, R. A., & Manjunath, N. (2005). CD70+ antigen-presenting cells control the proliferation and differentiation of T cells in the intestinal mucosa. Nature Immunology, 6, 698–706.
Lathrop, S. K., Bloom, S. M., Rao, S. M., Nutsch, K., Lio, C. W., Santacruz, N., Peterson, D. A., Stappenbeck, T. S., & Hsieh, C. S. (2011). Peripheral education of the immune system by colonic commensal microbiota. Nature, 478, 250–254.
LeibundGut-Landmann, S., Gross, O., Robinson, M. J., Osorio, F., Slack, E. C., Tsoni, S. V., Schweighoffer, E., Tybulewicz, V., Brown, G. D., Ruland, J., & Reis e Sousa, C. (2007). Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17. Nature Immunology, 8, 630–638.
Leung, J. M., Davenport, M., Wolff, M. J., Wiens, K. E., Abidi, W. M., Poles, M. A., Cho, I., Ullman, T., Mayer, L., & Loke, P. (2014). IL-22-producing CD4+ cells are depleted in actively inflamed colitis tissue. Mucosal Immunology, 7, 124–133.
Littman, D. R., & Rudensky, A. Y. (2010). Th17 and regulatory T cells in mediating and restraining inflammation. Cell, 140, 845–858.
Lukacs-Kornek, V., Malhotra, D., Fletcher, A. L., Acton, S. E., Elpek, K. G., Tayalia, P., Collier, A. R., & Turley, S. J. (2011). Regulated release of nitric oxide by nonhematopoietic stroma controls expansion of the activated T cell pool in lymph nodes. Nature Immunology, 12, 1096–1104.
Macatonia, S. E., Hosken, N. A., Litton, M., Vieira, P., Hsieh, C. S., Culpepper, J. A., Wysocka, M., Trinchieri, G., Murphy, K. M., & O’Garra, A. (1995). Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells. Journal of Immunology, 154, 5071–5079.
Malhotra, D., Fletcher, A. L., Astarita, J., Lukacs-Kornek, V., Tayalia, P., Gonzalez, S. F., Elpek, K. G., Chang, S. K., Knoblich, K., Hemler, M. E., et al. (2012). Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks. Nature Immunology, 13, 499–510.
Matteoli, G., Mazzini, E., Iliev, I. D., Mileti, E., Fallarino, F., Puccetti, P., Chieppa, M., & Rescigno, M. (2010). Gut CD103+ dendritic cells express indoleamine 2,3-dioxygenase which influences T regulatory/T effector cell balance and oral tolerance induction. Gut, 59, 595–604.
Matzinger, P., & Kamala, T. (2011). Tissue-based class control: The other side of tolerance. Nature Reviews Immunology, 11, 221–230.
Mazmanian, S. K., Liu, C. H., Tzianabos, A. O., & Kasper, D. L. (2005). An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell, 122, 107–118.
Mazmanian, S. K., Round, J. L., & Kasper, D. L. (2008). A microbial symbiosis factor prevents intestinal inflammatory disease. Nature, 453, 620–625.
McGovern, D., & Powrie, F. (2007). The IL23 axis plays a key role in the pathogenesis of IBD. Gut, 56, 1333–1336.
McGovern, D. P., Gardet, A., Torkvist, L., Goyette, P., Essers, J., Taylor, K. D., Neale, B. M., Ong, R. T., Lagace, C., Li, C., et al. (2010). Genome-wide association identifies multiple ulcerative colitis susceptibility loci. Nature Genetics, 42, 332–337.
Medzhitov, R. (2007). Recognition of microorganisms and activation of the immune response. Nature, 449, 819–826.
Mee, A. S., McLaughlin, J. E., Hodgson, H. J. F., & Jewell, D. P. (1979). Chronic immune colitis in rabbits. Gut Microbes, 20(1), 1–5.
Merad, M., Sathe, P., Helft, J., Miller, J., & Mortha, A. (2013). The dendritic cell lineage: Ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annual Review of Immunology, 31, 563–604.
Mestecky, J., McGhee, J. R., Bienenstock, J., Lamm, M. E., Strober, W., Cebra, J. J., Mayer, L., Pearay, L. O., & Russel, M. W. (2015). Historical aspects of mucosal immunology, vol 4.
Molenaar, R., Greuter, M., van der Marel, A. P., Roozendaal, R., Martin, S. F., Edele, F., Huehn, J., Forster, R., O’Toole, T., Jansen, W., et al. (2009). Lymph node stromal cells support dendritic cell-induced gut-homing of T cells. Journal of Immunology, 183, 6395–6402.
Molenaar, R., Knippenberg, M., Goverse, G., Olivier, B. J., de Vos, A. F., O’Toole, T., & Mebius, R. E. (2011). Expression of retinaldehyde dehydrogenase enzymes in mucosal dendritic cells and gut-draining lymph node stromal cells is controlled by dietary vitamin A. Journal of Immunology, 186, 1934–1942.
Mosmann, T. R., & Coffman, R. L. (1989). TH1 and TH2 cells: Different patterns of lymphokine secretion lead to different functional properties. Annual Review of Immunology, 7, 145–173.
Mowat, A. M., & Agace, W. W. (2014). Regional specialization within the intestinal immune system. Nature Reviews Immunology, 14, 667–685.
Mucida, D., Park, Y., Kim, G., Turovskaya, O., Scott, I., Kronenberg, M., & Cheroutre, H. (2007). Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science, 317, 256–260.
Murai, M., Turovskaya, O., Kim, G., Madan, R., Karp, C. L., Cheroutre, H., & Kronenberg, M. (2009). Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis. Nature Immunology, 10, 1178–1184.
Nawaf, M. G., Ulvmar, M. H., Withers, D. R., McConnell, F. M., Gaspal, F. M., Webb, G. J., Jones, N. D., Yagita, H., Allison, J. P., & Lane, P. J. L. (2017). Concurrent OX40 and CD30 ligand blockade abrogates the CD4-driven autoimmunity associated with CTLA4 and PD1 blockade while preserving excellent anti-CD8 tumor immunity. Journal of Immunology, 199, 974–981.
Neurath, M. F. (2014). Cytokines in inflammatory bowel disease. Nature Reviews Immunology, 14, 329–342.
Ohkura, N., Hamaguchi, M., Morikawa, H., Sugimura, K., Tanaka, A., Ito, Y., Osaki, M., Tanaka, Y., Yamashita, R., Nakano, N., et al. (2012). T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development. Immunity, 37, 785–799.
Ohnmacht, C., Park, J. H., Cording, S., Wing, J. B., Atarashi, K., Obata, Y., Gaboriau-Routhiau, V., Marques, R., Dulauroy, S., Fedoseeva, M., et al. (2015). Mucosal immunology. The microbiota regulates type 2 immunity through RORγt+ T cells. Science, 349, 989–993.
Onderdonk, A. B., Hermos, J. A., Dzink, J. L., & Bartlett, J. G. (1978). Protective effect of metronidazole in experimental ulcerative colitis. Gastroenterology, 74, 521–526.
Pabst, O., & Bernhardt, G. (2013). On the road to tolerance-generation and migration of gut regulatory T cells. European Journal of Immunology, 43, 1422–1425.
Pandiyan, P., Zheng, L., Ishihara, S., Reed, J., & Lenardo, M. J. (2007). CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells. Nature Immunology, 8, 1353–1362.
Panea, C., Farkas, A. M., Goto, Y., Abdollahi-Roodsaz, S., Lee, C., Koscso, B., Gowda, K., Hohl, T. M., Bogunovic, M., & Ivanov, I. I. (2015). Intestinal monocyte-derived macrophages control commensal-specific Th17 responses. Cell Reports, 12, 1314–1324.
Park, H. J., Park, J. S., Jeong, Y. H., Son, J., Ban, Y. H., Lee, B. H., Chen, L., Chang, J., Chung, D. H., Choi, I., & Ha, S. J. (2015). PD-1 upregulated on regulatory T cells during chronic virus infection enhances the suppression of CD8+ T cell immune response via the interaction with PD-L1 expressed on CD8+ T cells. Journal of Immunology, 194, 5801–5811.
Parks, O. B., Pociask, D. A., Hodzic, Z., Kolls, J. K., & Good, M. (2015). Interleukin-22 signaling in the regulation of intestinal health and disease. Frontiers in Cell and Development Biology, 3, 85.
Paul, W. E., & Zhu, J. (2010). How are T(H)2-type immune responses initiated and amplified? Nature Reviews Immunology, 10, 225–235.
Perlmann, P., & Broberger, O. (1963). In vitro studies of ulcerative colitis. II. Cytotoxic action of white blood cells from patients on human fetal colon cells. The Journal of Experimental Medicine, 117, 717–733.
Pezoldt, J., & Huehn, J. (2016). Tissue-specific induction of CCR6 and Nrp1 during early CD4+ T cell differentiation. European Journal of Microbiology & Immunology, 6, 219–226.
Polansky, J. K., Kretschmer, K., Freyer, J., Floess, S., Garbe, A., Baron, U., Olek, S., Hamann, A., von Boehmer, H., & Huehn, J. (2008). DNA methylation controls Foxp3 gene expression. European Journal of Immunology, 38, 1654–1663.
Powrie, F., Leach, M. W., Mauze, S., Caddle, L. B., & Coffman, R. L. (1993). Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 scid mice. International Immunology, 5, 1461–1471.
Powrie, F., Correa Oliveira, R., Mauze, S., & Coffman, R. L. (1994). Regulatory interactions between CD45RBhigh and CD45RBlow CD4+ T cells are important for the balance between protective and pathogenic cell-mediated immunity. The Journal of Experimental Medicine, 179, 589–600.
Radtke, A. J., Kastenmuller, W., Espinosa, D. A., Gerner, M. Y., Tse, S. W., Sinnis, P., Germain, R. N., Zavala, F. P., & Cockburn, I. A. (2015). Lymph-node resident CD8a+ dendritic cells capture antigens from migratory malaria sporozoites and induce CD8+ T cell responses. PLoS Pathogens, 11, e1004637.
Raverdeau, M., & Mills, K. H. (2014). Modulation of T cell and innate immune responses by retinoic acid. Journal of Immunology, 192, 2953–2958.
Roozendaal, R., Mempel, T. R., Pitcher, L. A., Gonzalez, S. F., Verschoor, A., Mebius, R. E., von Andrian, U. H., & Carroll, M. C. (2009). Conduits mediate transport of low-molecular-weight antigen to lymph node follicles. Immunity, 30, 264–276.
Rothenberg, E. V., Moore, J. E., & Yui, M. A. (2008). Launching the T-cell-lineage developmental programme. Nature Reviews Immunology, 8, 9–21.
Round, J. L., & Mazmanian, S. K. (2009). The gut microbiota shapes intestinal immune responses during health and disease. Nature Reviews Immunology, 9, 313–323.
Rovedatti, L., Kudo, T., Biancheri, P., Sarra, M., Knowles, C. H., Rampton, D. S., Corazza, G. R., Monteleone, G., Di Sabatino, A., & Macdonald, T. T. (2009). Differential regulation of interleukin 17 and interferon-γ production in inflammatory bowel disease. Gut, 58, 1629–1636.
Roy, U., Galvez, E. J. C., Iljazovic, A., Lesker, T. R., Blazejewski, A. J., Pils, M. C., Heise, U., Huber, S., Flavell, R. A., & Strowig, T. (2017). Distinct microbial communities trigger colitis development upon intestinal barrier damage via innate or adaptive immune cells. Cell Reports, 21, 994–1008.
Sakaguchi, S., Yamaguchi, T., Nomura, T., & Ono, M. (2008). Regulatory T cells and immune tolerance. Cell, 133, 775–787.
Schaper, K., Kietzmann, M., & Baumer, W. (2014). Sphingosine-1-phosphate differently regulates the cytokine production of IL-12, IL-23 and IL-27 in activated murine bone marrow derived dendritic cells. Molecular Immunology, 59, 10–18.
Schiering, C., Krausgruber, T., Chomka, A., Frohlich, A., Adelmann, K., Wohlfert, E. A., Pott, J., Griseri, T., Bollrath, J., Hegazy, A. N., et al. (2014). The alarmin IL-33 promotes regulatory T-cell function in the intestine. Nature, 513, 564–568.
Schulz, O., Jaensson, E., Persson, E. K., Liu, X., Worbs, T., Agace, W. W., & Pabst, O. (2009). Intestinal CD103+, but not CX3CR1+, antigen sampling cells migrate in lymph and serve classical dendritic cell functions. The Journal of Experimental Medicine, 206, 3101–3114.
Scott, C. L., Aumeunier, A. M., & Mowat, A. M. (2011). Intestinal CD103+ dendritic cells: Master regulators of tolerance? Trends in Immunology, 32, 412–419.
Sefik, E., Geva-Zatorsky, N., Oh, S., Konnikova, L., Zemmour, D., McGuire, A. M., Burzyn, D., Ortiz-Lopez, A., Lobera, M., Yang, J., et al. (2015). Mucosal immunology. Individual intestinal symbionts induce a distinct population of RORγ+ regulatory T cells. Science, 349, 993–997.
Shan, M., Gentile, M., Yeiser, J. R., Walland, A. C., Bornstein, V. U., Chen, K., He, B., Cassis, L., Bigas, A., Cols, M., et al. (2013). Mucus enhances gut homeostasis and oral tolerance by delivering immunoregulatory signals. Science, 342, 447–453.
Shevach, E. M. (2009). Mechanisms of foxp3+ T regulatory cell-mediated suppression. Immunity, 30, 636–645.
Shih, D. Q., Targan, S. R., & McGovern, D. (2008). Recent advances in IBD pathogenesis: Genetics and immunobiology. Current Gastroenterology Reports, 10, 8.
Shorter, R. G., Huizenga, K. A., ReMine, S. G., & Spencer, R. J. (1970). Effects of preliminary incubation of lymphocytes with serum on their cytotoxicity for colonic epithelial cells. Gastroenterology, 58, 843–850.
Siegert, S., Huang, H. Y., Yang, C. Y., Scarpellino, L., Carrie, L., Essex, S., Nelson, P. J., Heikenwalder, M., Acha-Orbea, H., Buckley, C. D., et al. (2011). Fibroblastic reticular cells from lymph nodes attenuate T cell expansion by producing nitric oxide. PLoS One, 6, e27618.
Siewert, C., Menning, A., Dudda, J., Siegmund, K., Lauer, U., Floess, S., Campbell, D. J., Hamann, A., & Huehn, J. (2007). Induction of organ-selective CD4+ regulatory T cell homing. European Journal of Immunology, 37, 978–989.
Singh, N., Gurav, A., Sivaprakasam, S., Brady, E., Padia, R., Shi, H., Thangaraju, M., Prasad, P. D., Manicassamy, S., Munn, D. H., et al. (2014). Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity, 40, 128–139.
Sixt, M., Kanazawa, N., Selg, M., Samson, T., Roos, G., Reinhardt, D. P., Pabst, R., Lutz, M. B., & Sorokin, L. (2005). The conduit system transports soluble antigens from the afferent lymph to resident dendritic cells in the T cell area of the lymph node. Immunity, 22, 19–29.
Smigiel, K. S., Srivastava, S., Stolley, J. M., & Campbell, D. J. (2014). Regulatory T-cell homeostasis: Steady-state maintenance and modulation during inflammation. Immunological Reviews, 259, 40–59.
Smith, P. M., Howitt, M. R., Panikov, N., Michaud, M., Gallini, C. A., Bohlooly, Y. M., Glickman, J. N., & Garrett, W. S. (2013). The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science, 341, 569–573.
Smyth, L. A., Ratnasothy, K., Tsang, J. Y., Boardman, D., Warley, A., Lechler, R., & Lombardi, G. (2013). CD73 expression on extracellular vesicles derived from CD4+CD25+Foxp3+ T cells contributes to their regulatory function. European Journal of Immunology, 43, 2430–2440.
Solomon, B. D., & Hsieh, C. S. (2016). Antigen-specific development of mucosal Foxp3+RORγt+ T cells from regulatory T cell precursors. Journal of Immunology, 197, 3512–3519.
Spadoni, I., Iliev, I. D., Rossi, G., & Rescigno, M. (2012). Dendritic cells produce TSLP that limits the differentiation of Th17 cells, fosters Treg development, and protects against colitis. Mucosal Immunology, 5, 184–193.
Sternberg, E. M. (2006). Neural regulation of innate immunity: A coordinated nonspecific host response to pathogens. Nature Reviews Immunology, 6, 318–328.
Sugihara, T., Kobori, A., Imaeda, H., Tsujikawa, T., Amagase, K., Takeuchi, K., Fujiyama, Y., & Andoh, A. (2010). The increased mucosal mRNA expressions of complement C3 and interleukin-17 in inflammatory bowel disease. Clinical and Experimental Immunology, 160, 386–393.
Sun, C. M., Hall, J. A., Blank, R. B., Bouladoux, N., Oukka, M., Mora, J. R., & Belkaid, Y. (2007). Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 Treg cells via retinoic acid. The Journal of Experimental Medicine, 204, 1775–1785.
Szabo, S. J., Kim, S. T., Costa, G. L., Zhang, X., Fathman, C. G., & Glimcher, L. H. (2000). A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell, 100, 655–669.
Tartar, D. M., VanMorlan, A. M., Wan, X., Guloglu, F. B., Jain, R., Haymaker, C. L., Ellis, J. S., Hoeman, C. M., Cascio, J. A., Dhakal, M., et al. (2010). FoxP3+RORγt+ T helper intermediates display suppressive function against autoimmune diabetes. Journal of Immunology, 184, 3377–3385.
Toker, A., Engelbert, D., Garg, G., Polansky, J. K., Floess, S., Miyao, T., Baron, U., Duber, S., Geffers, R., Giehr, P., et al. (2013). Active demethylation of the Foxp3 locus leads to the generation of stable regulatory T cells within the thymus. Journal of Immunology, 190, 3180–3188.
Tone, Y., Furuuchi, K., Kojima, Y., Tykocinski, M. L., Greene, M. I., & Tone, M. (2008). Smad3 and NFAT cooperate to induce Foxp3 expression through its enhancer. Nature Immunology, 9, 194–202.
Torow, N., Yu, K., Hassani, K., Freitag, J., Schulz, O., Basic, M., Brennecke, A., Sparwasser, T., Wagner, N., Bleich, A., et al. (2015). Active suppression of intestinal CD4+TCRab+ T-lymphocyte maturation during the postnatal period. Nature Communications, 6, 7725.
Trifari, S., Kaplan, C. D., Tran, E. H., Crellin, N. K., & Spits, H. (2009). Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from T(H)-17, T(H)1 and T(H)2 cells. Nature Immunology, 10, 864–871.
Trinchieri, G. (1994). Interleukin-12: A cytokine produced by antigen-presenting cells with immunoregulatory functions in the generation of T-helper cells type 1 and cytotoxic lymphocytes. Blood, 84, 20.
Vantourout, P., & Hayday, A. (2013). Six-of-the-best: Unique contributions of gdT cells to immunology. Nature Reviews Immunology, 13, 88–100.
Vignali, D. A., Collison, L. W., & Workman, C. J. (2008). How regulatory T cells work. Nature Reviews Immunology, 8, 523–532.
Weber, B., Saurer, L., Schenk, M., Dickgreber, N., & Mueller, C. (2011). CX3CR1 defines functionally distinct intestinal mononuclear phagocyte subsets which maintain their respective functions during homeostatic and inflammatory conditions. European Journal of Immunology, 41, 773–779.
Weinreich, M. A., & Hogquist, K. A. (2008). Thymic emigration: When and how T cells leave home. Journal of Immunology, 181, 2265–2270.
Winau, F., Quack, C., Darmoise, A., & Kaufmann, S. H. (2008). Starring stellate cells in liver immunology. Current Opinion in Immunology, 20, 68–74.
Wohlfert, E. A., Grainger, J. R., Bouladoux, N., Konkel, J. E., Oldenhove, G., Ribeiro, C. H., Hall, J. A., Yagi, R., Naik, S., Bhairavabhotla, R., et al. (2011). GATA3 controls Foxp3+ regulatory T cell fate during inflammation in mice. The Journal of Clinical Investigation, 121, 4503–4515.
Wolvers, D. A., Coenen-de Roo, C. J., Mebius, R. E., van der Cammen, M. J., Tirion, F., Miltenburg, A. M., & Kraal, G. (1999). Intranasally induced immunological tolerance is determined by characteristics of the draining lymph nodes: Studies with OVA and human cartilage gp-39. Journal of Immunology, 162, 1994–1998.
Worbs, T., Bode, U., Yan, S., Hoffmann, M. W., Hintzen, G., Bernhardt, G., Forster, R., & Pabst, O. (2006). Oral tolerance originates in the intestinal immune system and relies on antigen carriage by dendritic cells. The Journal of Experimental Medicine, 203, 519–527.
Yang, B. H., Hagemann, S., Mamareli, P., Lauer, U., Hoffmann, U., Beckstette, M., Fohse, L., Prinz, I., Pezoldt, J., Suerbaum, S., et al. (2016). Foxp3+ T cells expressing RORγt represent a stable regulatory T-cell effector lineage with enhanced suppressive capacity during intestinal inflammation. Mucosal Immunology, 9, 444–457.
Ye, P., Rodriguez, F. H., Kanaly, S., Stocking, K. L., Schurr, J., Schwarzenberger, P., Oliver, P., Huang, W., Zhang, P., Zhang, J., et al. (2001). Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. The Journal of Experimental Medicine, 194, 519–527.
Zechner, E. L. (2017). Inflammatory disease caused by intestinal pathobionts. Current Opinion in Microbiology, 35, 64–69.
Zhang, Z., Zhang, W., Guo, J., Gu, Q., Zhu, X., & Zhou, X. (2017). Activation and functional specialization of regulatory T cells lead to the generation of Foxp3 instability. Journal of Immunology, 198, 2612–2625.
Zheng, W., & Flavell, R. A. (1997). The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell, 89, 587–596.
Zheng, S. G., Wang, J. H., Stohl, W., Kim, K. S., Gray, J. D., & Horwitz, D. A. (2006). TGF-beta requires CTLA-4 early after T cell activation to induce FoxP3 and generate adaptive CD4+CD25+ regulatory cells. Journal of Immunology, 176, 3321–3329.
Zheng, Y., Josefowicz, S., Chaudhry, A., Peng, X. P., Forbush, K., & Rudensky, A. Y. (2010). Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature, 463, 808–812.
Zigmond, E., Varol, C., Farache, J., Elmaliah, E., Satpathy, A. T., Friedlander, G., Mack, M., Shpigel, N., Boneca, I. G., Murphy, K. M., et al. (2012). Ly6Chi monocytes in the inflamed colon give rise to proinflammatory effector cells and migratory antigen-presenting cells. Immunity, 37, 1076–1090.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG, part of Springer Nature
About this chapter
Cite this chapter
Pezoldt, J., Yang, J., Zou, M., Huehn, J. (2018). Microbiome and Gut Immunity: T Cells. In: Haller, D. (eds) The Gut Microbiome in Health and Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-90545-7_9
Download citation
DOI: https://doi.org/10.1007/978-3-319-90545-7_9
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-90544-0
Online ISBN: 978-3-319-90545-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)