The Special Relationship in the Development and Function of T Helper 17 and Regulatory T Cells

Progress in Molecular Biology and Translational Science

Volumn 136, Issue , 2015, Pages 99-129

  Lochner, Matthias ^a   Wang, Zuobai ^a   Sparwasser, Tim ^a  

^a INSTITUTE OF INFECTION IMMUNOLOGY   (Germany)

Author keywords

Immune regulation; Infection; Inflammation; Regulatory T cells; T helper 17 cells

Indexed keywords

CYTOKINE; INTERLEUKIN 17; RETINOID RELATED ORPHAN RECEPTOR GAMMA; TRANSCRIPTION FACTOR FOXP3;

BACTERIAL INFECTION; CD4+ T LYMPHOCYTE; CELL LINEAGE; CELL MATURATION; CELL PLASTICITY; CELLULAR IMMUNITY; CONFERENCE PAPER; CYTOKINE RELEASE; HUMAN; IMMUNOPHENOTYPING; IN VIVO STUDY; INFLAMMATION; LYMPHOCYTE DIFFERENTIATION; LYMPHOCYTE FUNCTION; MYCOSIS; NONHUMAN; PHYSIOLOGICAL PROCESS; PRIORITY JOURNAL; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE SUBPOPULATION; TH17 CELL; TISSUE INJURY; ANIMAL; BIOLOGICAL MODEL; CYTOLOGY;

ANIMALS; HUMANS; MODELS, IMMUNOLOGICAL; T-LYMPHOCYTES, REGULATORY; TH17 CELLS;

EID: 84939864934     PISSN: 18771173     EISSN: 18780814     Source Type: Book Series    
DOI: 10.1016/bs.pmbts.2015.07.013     Document Type: Conference Paper

References (203)

1. L.E. Harrington, R.D. Hatton, P.R. Mangan, and et al. Interleukin 17-producing CD4 + effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages Nat Immunol 6 11 2005 1123 1132
2. C.L. Langrish, Y. Chen, W.M. Blumenschein, and et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation J Exp Med 201 2 2005 233 240
3. H. Park, Z. Li, X.O. Yang, and et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17 Nat Immunol 6 11 2005 1133 1141
4. T. Aarvak, M. Chabaud, P. Miossec, and J.B. Natvig IL-17 is produced by some proinflammatory Th1/Th0 cells but not by Th2 cells J Immunol 162 3 1999 1246 1251
5. C. Infante-Duarte, H.F. Horton, M.C. Byrne, and T. Kamradt Microbial lipopeptides induce the production of IL-17 in Th cells J Immunol 165 11 2000 6107 6115
6. D.J. Cua, and C.M. Tato Innate IL-17-producing cells: the sentinels of the immune system Nat Rev Immunol 10 7 2010 479 489
7. M.L. Michel, D. Mendes-da-Cruz, A.C. Keller, and et al. Critical role of ROR-gammat in a new thymic pathway leading to IL-17-producing invariant NKT cell differentiation Proc Natl Acad Sci USA 105 50 2008 19845 19850
8. G. Eberl, M. Colonna, J.P. Di Santo, and A.N. McKenzie Innate lymphoid cells. Innate lymphoid cells: a new paradigm in immunology Science 348 6237 2015 aaa6566
9. D.J. Cua, J. Sherlock, Y. Chen, and et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain Nature 421 6924 2003 744 748
10. E. Bettelli, Y. Carrier, W. Gao, and et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells Nature 441 7090 2006 235 238
11. P.R. Mangan, L.E. Harrington, D.B. O'Quinn, and et al. Transforming growth factor-beta induces development of the T(H)17 lineage Nature 441 7090 2006 231 234
12. M. Veldhoen, R.J. Hocking, C.J. Atkins, R.M. Locksley, and B. Stockinger TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells Immunity 24 2 2006 179 189
13. L. Durant, W.T. Watford, H.L. Ramos, and et al. Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis Immunity 32 5 2010 605 615
14. M.A. Ortiz, F.J. Piedrafita, M. Pfahl, and R. Maki TOR: a new orphan receptor expressed in the thymus that can modulate retinoid and thyroid hormone signals Mol Endocrinol 9 12 1995 1679 1691
15. J. Guo, A. Hawwari, H. Li, and et al. Regulation of the TCRalpha repertoire by the survival window of CD4(+)CD8(+) thymocytes Nat Immunol 3 5 2002 469 476
16. Y.W. He, C. Beers, M.L. Deftos, E.W. Ojala, K.A. Forbush, and M.J. Bevan Down-regulation of the orphan nuclear receptor ROR gamma t is essential for T lymphocyte maturation J Immunol 164 11 2000 5668 5674
17. Z. Sun, D. Unutmaz, Y.R. Zou, and et al. Requirement for RORgamma in thymocyte survival and lymphoid organ development Science 288 5475 2000 2369 2373
18. I. Villey, R. de Chasseval, and J.P. de Villartay RORgammaT, a thymus-specific isoform of the orphan nuclear receptor RORgamma/TOR, is up-regulated by signaling through the pre-T cell receptor and binds to the TEA promoter Eur J Immunol 29 12 1999 4072 4080
19. G. Eberl, S. Marmon, M.J. Sunshine, P.D. Rennert, Y. Choi, and D.R. Littman An essential function for the nuclear receptor RORgamma(t) in the generation of fetal lymphoid tissue inducer cells Nat Immunol 5 1 2004 64 73
20. S. Cording, J. Medvedovic, M. Cherrier, and G. Eberl Development and regulation of RORgammat(+) innate lymphoid cells FEBS Lett 588 22 2014 4176 4181
21. A. Diefenbach, M. Colonna, and S. Koyasu Development, differentiation, and diversity of innate lymphoid cells Immunity 41 3 2014 354 365
22. I.I. Ivanov, B.S. McKenzie, L. Zhou, and et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17 + T helper cells Cell 126 6 2006 1121 1133
23. M. Ciofani, A. Madar, C. Galan, and et al. A validated regulatory network for Th17 cell specification Cell 151 2 2012 289 303
24. T. Korn, M. Oukka, V. Kuchroo, and E. Bettelli Th17 cells: effector T cells with inflammatory properties Semin Immunol 19 6 2007 362 371
25. R. Nurieva, X.O. Yang, G. Martinez, and et al. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells Nature 448 7152 2007 480 483
26. Y. Chung, S.H. Chang, G.J. Martinez, and et al. Critical regulation of early Th17 cell differentiation by interleukin-1 signaling Immunity 30 4 2009 576 587
27. M.F. Gulen, Z. Kang, K. Bulek, and et al. The receptor SIGIRR suppresses Th17 cell proliferation via inhibition of the interleukin-1 receptor pathway and mTOR kinase activation Immunity 32 1 2010 54 66
28. L. Berod, C. Friedrich, A. Nandan, and et al. De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells Nat Med 20 11 2014 1327 1333
29. R.D. Michalek, V.A. Gerriets, S.R. Jacobs, and et al. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4 + T cell subsets J Immunol 186 6 2011 3299 3303
30. J.D. Powell, K.N. Pollizzi, E.B. Heikamp, and M.R. Horton Regulation of immune responses by mTOR Annu Rev Immunol 30 2012 39 68
31. E.V. Dang, J. Barbi, H.Y. Yang, and et al. Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1 Cell 146 5 2011 772 784
32. L.Z. Shi, R. Wang, G. Huang, and et al. HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells J Exp Med 208 7 2011 1367 1376
33. I. Gutcher, M.K. Donkor, Q. Ma, A.Y. Rudensky, R.A. Flavell, and M.O. Li Autocrine transforming growth factor-beta1 promotes in vivo Th17 cell differentiation Immunity 34 3 2011 396 408
34. M.O. Li, Y.Y. Wan, and R.A. Flavell T cell-produced transforming growth factor-beta1 controls T cell tolerance and regulates Th1- and Th17-cell differentiation Immunity 26 5 2007 579 591
35. M. Veldhoen, R.J. Hocking, R.A. Flavell, and B. Stockinger Signals mediated by transforming growth factor-beta initiate autoimmune encephalomyelitis, but chronic inflammation is needed to sustain disease Nat Immunol 7 11 2006 1151 1156
36. J. Das, G. Ren, L. Zhang, and et al. Transforming growth factor beta is dispensable for the molecular orchestration of Th17 cell differentiation J Exp Med 206 11 2009 2407 2416
37. K. Ghoreschi, A. Laurence, X.P. Yang, and et al. Generation of pathogenic T(H)17 cells in the absence of TGF-beta signalling Nature 467 7318 2010 967 971
38. M.J. McGeachy, K.S. Bak-Jensen, Y. Chen, and et al. TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology Nat Immunol 8 12 2007 1390 1397
39. C.J. Haines, Y. Chen, W.M. Blumenschein, and et al. Autoimmune memory T helper 17 cell function and expansion are dependent on interleukin-23 Cell Rep 3 5 2013 1378 1388
40. M.J. McGeachy, Y. Chen, C.M. Tato, and et al. The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo Nat Immunol 10 3 2009 314 324
41. E. Esplugues, S. Huber, N. Gagliani, and et al. Control of TH17 cells occurs in the small intestine Nature 475 7357 2011 514 518
42. C. Heinemann, S. Heink, F. Petermann, and et al. IL-27 and IL-12 oppose pro-inflammatory IL-23 in CD4 + T cells by inducing Blimp1 Nat Commun 5 2014 3770
43. Y. Lee, A. Awasthi, N. Yosef, and et al. Induction and molecular signature of pathogenic TH17 cells Nat Immunol 13 10 2012 991 999
44. K. Hirota, J.H. Duarte, M. Veldhoen, and et al. Fate mapping of IL-17-producing T cells in inflammatory responses Nat Immunol 12 3 2011 255 263
45. Y.K. Lee, H. Turner, C.L. Maynard, and et al. Late developmental plasticity in the T helper 17 lineage Immunity 30 1 2009 92 107
46. Y. Yang, J. Weiner, Y. Liu, and et al. T-bet is essential for encephalitogenicity of both Th1 and Th17 cells J Exp Med 206 7 2009 1549 1564
47. P.P. Ahern, C. Schiering, S. Buonocore, and et al. Interleukin-23 drives intestinal inflammation through direct activity on T cells Immunity 33 2 2010 279 288
48. A.M. Globig, N. Hennecke, B. Martin, and et al. Comprehensive intestinal T helper cell profiling reveals specific accumulation of IFN-gamma+IL-17+coproducing CD4 + T cells in active inflammatory bowel disease Inflamm Bowel Dis 20 12 2014 2321 2329
49. S. Hue, P. Ahern, S. Buonocore, and et al. Interleukin-23 drives innate and T cell-mediated intestinal inflammation J Exp Med 203 11 2006 2473 2483
50. M.C. Kullberg, D. Jankovic, C.G. Feng, and et al. IL-23 plays a key role in Helicobacter hepaticus-induced T cell-dependent colitis J Exp Med 203 11 2006 2485 2494
51. D. Bending, S. Newland, A. Krejci, J.M. Phillips, S. Bray, and A. Cooke Epigenetic changes at Il12rb2 and Tbx21 in relation to plasticity behavior of Th17 cells J Immunol 186 6 2011 3373 3382
52. R. Mukasa, A. Balasubramani, Y.K. Lee, and et al. Epigenetic instability of cytokine and transcription factor gene loci underlies plasticity of the T helper 17 cell lineage Immunity 32 5 2010 616 627
53. G. Wei, L. Wei, J. Zhu, and et al. Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4 + T cells Immunity 30 1 2009 155 167
54. D. Bending, H. De la Pena, M. Veldhoen, and et al. Highly purified Th17 cells from BDC2.5NOD mice convert into Th1-like cells in NOD/SCID recipient mice J Clin Invest 119 3 2009 565 572
55. N. Martin-Orozco, Y. Chung, S.H. Chang, Y.H. Wang, and C. Dong Th17 cells promote pancreatic inflammation but only induce diabetes efficiently in lymphopenic hosts after conversion into Th1 cells Eur J Immunol 39 1 2009 216 224
56. A.L. Croxford, F.C. Kurschus, and A. Waisman Cutting edge: an IL-17F-CreEYFP reporter mouse allows fate mapping of Th17 cells J Immunol 182 3 2009 1237 1241
57. N. Gagliani, M.C. Vesely, A. Iseppon, and et al. Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation Nature 523 7559 2015 221 225
58. K. Hirota, J.E. Turner, M. Villa, and et al. Plasticity of Th17 cells in Peyer's patches is responsible for the induction of T cell-dependent IgA responses Nat Immunol 14 4 2013 372 379
59. P. Muranski, Z.A. Borman, S.P. Kerkar, and et al. Th17 cells are long lived and retain a stem cell-like molecular signature Immunity 35 6 2011 972 985
60. I. Kryczek, E. Zhao, Y. Liu, and et al. Human TH17 cells are long-lived effector memory cells Sci Transl Med 3 104 2011 104ra100
61. M. Lochner, L. Peduto, M. Cherrier, and et al. In vivo equilibrium of proinflammatory IL-17 + and regulatory IL-10 + Foxp3 + RORgamma t + T cells J Exp Med 205 6 2008 1381 1393
62. V. Gaboriau-Routhiau, S. Rakotobe, E. Lecuyer, and et al. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses Immunity 31 4 2009 677 689
63. I.I. Ivanov, K. Atarashi, N. Manel, and et al. Induction of intestinal Th17 cells by segmented filamentous bacteria Cell 139 3 2009 485 498
64. M. Lochner, M. Berard, S. Sawa, and et al. Restricted microbiota and absence of cognate TCR antigen leads to an unbalanced generation of Th17 cells J Immunol 186 3 2011 1531 1537
65. Y. Goto, C. Panea, G. Nakato, and et al. Segmented filamentous bacteria antigens presented by intestinal dendritic cells drive mucosal Th17 cell differentiation Immunity 40 4 2014 594 607
66. Y. Yang, M.B. Torchinsky, M. Gobert, and et al. Focused specificity of intestinal TH17 cells towards commensal bacterial antigens Nature 510 7503 2014 152 156
67. G.L. Talham, H.Q. Jiang, N.A. Bos, and J.J. Cebra Segmented filamentous bacteria are potent stimuli of a physiologically normal state of the murine gut mucosal immune system Infect Immun 67 4 1999 1992 2000
68. K. Atarashi, J. Nishimura, T. Shima, and et al. ATP drives lamina propria T(H)17 cell differentiation Nature 455 7214 2008 808 812
69. I.I. Ivanov, L. Frutos Rde, N. Manel, and et al. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine Cell Host Microbe 4 4 2008 337 349
70. K.L. Lewis, M.L. Caton, M. Bogunovic, and et al. Notch2 receptor signaling controls functional differentiation of dendritic cells in the spleen and intestine Immunity 35 5 2011 780 791
71. E.K. Persson, H. Uronen-Hansson, M. Semmrich, and et al. IRF4 transcription-factor-dependent CD103(+)CD11b(+) dendritic cells drive mucosal T helper 17 cell differentiation Immunity 38 5 2013 958 969
72. A.T. Satpathy, C.G. Briseno, J.S. Lee, and et al. Notch2-dependent classical dendritic cells orchestrate intestinal immunity to attaching-and-effacing bacterial pathogens Nat Immunol 14 9 2013 937 948
73. A. Schlitzer, N. McGovern, P. Teo, and et al. IRF4 transcription factor-dependent CD11b + dendritic cells in human and mouse control mucosal IL-17 cytokine responses Immunity 38 5 2013 970 983
74. N.E. Welty, C. Staley, N. Ghilardi, M.J. Sadowsky, B.Z. Igyarto, and D.H. Kaplan Intestinal lamina propria dendritic cells maintain T cell homeostasis but do not affect commensalism J Exp Med 210 10 2013 2011 2024
75. V. Cerovic, S.A. Houston, C.L. Scott, and et al. Intestinal CD103(-) dendritic cells migrate in lymph and prime effector T cells Mucosal Immunol 6 1 2013 104 113
76. K. Fujimoto, T. Karuppuchamy, N. Takemura, and et al. A new subset of CD103+CD8alpha + dendritic cells in the small intestine expresses TLR3, TLR7, and TLR9 and induces Th1 response and CTL activity J Immunol 186 11 2011 6287 6295
77. S. Uematsu, K. Fujimoto, M.H. Jang, and et al. Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5 Nat Immunol 9 7 2008 769 776
78. M.A. Kinnebrew, C.G. Buffie, G.E. Diehl, and et al. Interleukin 23 production by intestinal CD103(+)CD11b(+) dendritic cells in response to bacterial flagellin enhances mucosal innate immune defense Immunity 36 2 2012 276 287
79. M.H. Shaw, N. Kamada, Y.G. Kim, and G. Nunez Microbiota-induced IL-1beta, but not IL-6, is critical for the development of steady-state TH17 cells in the intestine J Exp Med 209 2 2012 251 258
80. F.J. Quintana, A.S. Basso, A.H. Iglesias, and et al. Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor Nature 453 7191 2008 65 71
81. M. Veldhoen, K. Hirota, A.M. Westendorf, and et al. The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins Nature 453 7191 2008 106 109
82. T. Nakahama, A. Kimura, N.T. Nguyen, and et al. Aryl hydrocarbon receptor deficiency in T cells suppresses the development of collagen-induced arthritis Proc Natl Acad Sci USA 108 34 2011 14222 14227
83. F.J. Quintana, G. Murugaiyan, M.F. Farez, and et al. An endogenous aryl hydrocarbon receptor ligand acts on dendritic cells and T cells to suppress experimental autoimmune encephalomyelitis Proc Natl Acad Sci USA 107 48 2010 20768 20773
84. Y. Li, S. Innocentin, D.R. Withers, and et al. Exogenous stimuli maintain intraepithelial lymphocytes via aryl hydrocarbon receptor activation Cell 147 3 2011 629 640
85. J. Qiu, X. Guo, Z.M. Chen, and et al. Group 3 innate lymphoid cells inhibit T-cell-mediated intestinal inflammation through aryl hydrocarbon receptor signaling and regulation of microflora Immunity 39 2 2013 386 399
86. S.A. Khader, S.L. Gaffen, and J.K. Kolls Th17 cells at the crossroads of innate and adaptive immunity against infectious diseases at the mucosa Mucosal Immunol 2 5 2009 403 411
87. J.K. Kolls, and S.A. Khader The role of Th17 cytokines in primary mucosal immunity Cytokine Growth Factor Rev 21 6 2010 443 448
88. R. Pappu, S. Rutz, and W. Ouyang Regulation of epithelial immunity by IL-17 family cytokines Trends Immunol 33 7 2012 343 349
89. G. Pickert, C. Neufert, M. Leppkes, and et al. STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing J Exp Med 206 7 2009 1465 1472
90. W. Ouyang, J.K. Kolls, and Y. Zheng The biological functions of T helper 17 cell effector cytokines in inflammation Immunity 28 4 2008 454 467
91. M. Pelletier, L. Maggi, A. Micheletti, and et al. Evidence for a cross-talk between human neutrophils and Th17 cells Blood 115 2 2009 335 343
92. P. Ye, F.H. Rodriguez, S. Kanaly, and et al. Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense J Exp Med 194 4 2001 519 527
93. J.D. Milner, N.G. Sandler, and D.C. Douek Th17 cells, Job's syndrome and HIV: opportunities for bacterial and fungal infections Curr Opin HIV AIDS 5 2 2010 179 183
94. M.L. Paulson, A.F. Freeman, and S.M. Holland Hyper IgE syndrome: an update on clinical aspects and the role of signal transducer and activator of transcription 3 Curr Opin Allergy Clin Immunol 8 6 2008 527 533
95. H.R. Conti, F. Shen, N. Nayyar, and et al. Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis J Exp Med 206 2 2009 299 311
96. A. Puel, S. Cypowyj, L. Marodi, L. Abel, C. Picard, and J.L. Casanova Inborn errors of human IL-17 immunity underlie chronic mucocutaneous candidiasis Curr Opin Allergy Clin Immunol 12 6 2012 616 622
97. M.C. Ferreira, N. Whibley, A.J. Mamo, U. Siebenlist, Y.R. Chan, and S.L. Gaffen Interleukin-17-induced protein lipocalin 2 is dispensable for immunity to oral candidiasis Infect Immun 82 3 2014 1030 1035
98. A.W. Ho, F. Shen, H.R. Conti, and et al. IL-17RC is required for immune signaling via an extended SEF/IL-17R signaling domain in the cytoplasmic tail J Immunol 185 2 2010 1063 1070
99. S. Kagami, H.L. Rizzo, S.E. Kurtz, L.S. Miller, and A. Blauvelt IL-23 and IL-17A, but not IL-12 and IL-22, are required for optimal skin host defense against Candida albicans J Immunol 185 9 2010 5453 5462
100. W. Huang, L. Na, P.L. Fidel, and P. Schwarzenberger Requirement of interleukin-17A for systemic anti-Candida albicans host defense in mice J Infect Dis 190 3 2004 624 631
101. S. Saijo, S. Ikeda, K. Yamabe, and et al. Dectin-2 recognition of alpha-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans Immunity 32 5 2010 681 691
102. F.L. van de Veerdonk, B.J. Kullberg, I.C. Verschueren, and et al. Differential effects of IL-17 pathway in disseminated candidiasis and zymosan-induced multiple organ failure Shock 34 4 2010 407 411
103. N. Whibley, and S.L. Gaffen Brothers in arms: Th17 and Treg responses in Candida albicans immunity PLoS Pathog 10 12 2014 e1004456
104. N. Hernandez-Santos, A.R. Huppler, A.C. Peterson, S.A. Khader, K.C. McKenna, and S.L. Gaffen Th17 cells confer long-term adaptive immunity to oral mucosal Candida albicans infections Mucosal Immunol 6 5 2013 900 910
105. E.L. Symonds, C.U. Riedel, D. O'Mahony, S. Lapthorne, L. O'Mahony, and F. Shanahan Involvement of T helper type 17 and regulatory T cell activity in Citrobacter rodentium invasion and inflammatory damage Clin Exp Immunol 157 1 2009 148 154
106. H. Ishigame, S. Kakuta, T. Nagai, and et al. Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses Immunity 30 1 2009 108 119
107. M. Cella, A. Fuchs, W. Vermi, and et al. A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity Nature 457 7230 2009 722 725
108. S.L. Sanos, V.L. Bui, A. Mortha, and et al. RORgammat and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46 + cells Nat Immunol 10 1 2009 83 91
109. N. Satoh-Takayama, C.A. Vosshenrich, S. Lesjean-Pottier, and et al. Microbial flora drives interleukin 22 production in intestinal NKp46 + cells that provide innate mucosal immune defense Immunity 29 6 2008 958 970
110. G.F. Sonnenberg, L.A. Monticelli, M.M. Elloso, L.A. Fouser, and D. Artis CD4(+) lymphoid tissue-inducer cells promote innate immunity in the gut Immunity 34 1 2011 122 134
111. Y. Zheng, P.A. Valdez, D.M. Danilenko, and et al. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens Nat Med 14 3 2008 282 289
112. C. Manta, E. Heupel, K. Radulovic, and et al. CX(3)CR1(+) macrophages support IL-22 production by innate lymphoid cells during infection with Citrobacter rodentium Mucosal Immunol 6 1 2013 177 188
113. K. Geddes, S.J. Rubino, J.G. Magalhaes, and et al. Identification of an innate T helper type 17 response to intestinal bacterial pathogens Nat Med 17 7 2011 837 844
114. T. Zelante, A. De Luca, P. Bonifazi, and et al. IL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistance Eur J Immunol 37 10 2007 2695 2706
115. R. Caruso, D. Fina, O.A. Paoluzi, and et al. IL-23-mediated regulation of IL-17 production in Helicobacter pylori-infected gastric mucosa Eur J Immunol 38 2 2008 470 478
116. F. Luzza, T. Parrello, G. Monteleone, and et al. Up-regulation of IL-17 is associated with bioactive IL-8 expression in Helicobacter pylori-infected human gastric mucosa J Immunol 165 9 2000 5332 5337
117. E.E. Way, K. Chen, and J.K. Kolls Dysregulation in lung immunity - the protective and pathologic Th17 response in infection Eur J Immunol 43 12 2013 3116 3124
118. S. Wiehler, and D. Proud Interleukin-17A modulates human airway epithelial responses to human rhinovirus infection Am J Physiol Lung Cell Mol Physiol 293 2 2007 L505 L515
119. R.P. Singh, S. Hasan, S. Sharma, and et al. Th17 cells in inflammation and autoimmunity Autoimmun Rev 13 12 2014 1174 1181
120. S.L. Gaffen, R. Jain, A.V. Garg, and D.J. Cua The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing Nat Rev Immunol 14 9 2014 585 600
121. W. Hueber, B.E. Sands, S. Lewitzky, and et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn's disease: unexpected results of a randomised, double-blind placebo-controlled trial Gut 61 12 2012 1693 1700
122. S.R. Targan, B.G. Feagan, S. Vermeire, and et al. A randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and efficacy of AMG 827 in subjects with moderate to severe Crohn's disease Gastroenterology 143 3 2012 E26
123. R.H. Duerr, K.D. Taylor, S.R. Brant, and et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene Science 314 5804 2006 1461 1463
124. W. O'Connor Jr., M. Kamanaka, C.J. Booth, and et al. A protective function for interleukin 17A in T cell-mediated intestinal inflammation Nat Immunol 10 6 2009 603 609
125. A. Ogawa, A. Andoh, Y. Araki, T. Bamba, and Y. Fujiyama Neutralization of interleukin-17 aggravates dextran sulfate sodium-induced colitis in mice Clin Immunol 110 1 2004 55 62
126. T. Yi, D. Zhao, C.L. Lin, and et al. Absence of donor Th17 leads to augmented Th1 differentiation and exacerbated acute graft-versus-host disease Blood 112 5 2008 2101 2110
127. S. Sakaguchi, N. Sakaguchi, M. Asano, M. Itoh, and M. Toda Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases J Immunol 155 3 1995 1151 1164
128. L.B. Clark, M.W. Appleby, M.E. Brunkow, J.E. Wilkinson, S.F. Ziegler, and F. Ramsdell Cellular and molecular characterization of the scurfy mouse mutant J Immunol 162 5 1999 2546 2554
129. M.F. Lyon, J. Peters, P.H. Glenister, S. Ball, and E. Wright The scurfy mouse mutant has previously unrecognized hematological abnormalities and resembles Wiskott-Aldrich syndrome Proc Natl Acad Sci USA 87 7 1990 2433 2437
130. R.S. Wildin, F. Ramsdell, J. Peake, and et al. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy Nat Genet 27 1 2001 18 20
131. C.L. Bennett, J. Christie, F. Ramsdell, and et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3 Nat Genet 27 1 2001 20 21
132. M.E. Brunkow, E.W. Jeffery, K.A. Hjerrild, and et al. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse Nat Genet 27 1 2001 68 73
133. J.D. Fontenot, J.P. Rasmussen, L.M. Williams, J.L. Dooley, A.G. Farr, and A.Y. Rudensky Regulatory T cell lineage specification by the forkhead transcription factor foxp3 Immunity 22 3 2005 329 341
134. S. Hori, T. Nomura, and S. Sakaguchi Control of regulatory T cell development by the transcription factor Foxp3 Science 299 5609 2003 1057 1061
135. J.M. Kim, J.P. Rasmussen, and A.Y. Rudensky Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice Nat Immunol 8 2 2007 191 197
136. K. Lahl, C. Loddenkemper, C. Drouin, and et al. Selective depletion of Foxp3 + regulatory T cells induces a scurfy-like disease J Exp Med 204 1 2007 57 63
137. J. Suffner, K. Hochweller, M.C. Kuhnle, and et al. Dendritic cells support homeostatic expansion of Foxp3 + regulatory T cells in Foxp3.LuciDTR mice J Immunol 184 4 2010 1810 1820
138. L. Berod, F. Puttur, J. Huehn, and T. Sparwasser Tregs in infection and vaccinology: heroes or traitors? Microb Biotechnol 5 2 2012 260 269
139. J. Kim, K. Lahl, S. Hori, and et al. Cutting edge: depletion of Foxp3 + cells leads to induction of autoimmunity by specific ablation of regulatory T cells in genetically targeted mice J Immunol 183 12 2009 7631 7634
140. K. Klages, C.T. Mayer, K. Lahl, and et al. Selective depletion of Foxp3 + regulatory T cells improves effective therapeutic vaccination against established melanoma Cancer Res 70 20 2010 7788 7799
141. D. Haribhai, W. Lin, B. Edwards, and et al. A central role for induced regulatory T cells in tolerance induction in experimental colitis J Immunol 182 6 2009 3461 3468
142. S.Z. Josefowicz, R.E. Niec, H.Y. Kim, and et al. Extrathymically generated regulatory T cells control mucosal TH2 inflammation Nature 482 7385 2012 395 399
143. S.K. Lathrop, S.M. Bloom, S.M. Rao, and et al. Peripheral education of the immune system by colonic commensal microbiota Nature 478 7368 2011 250 254
144. R.M. Samstein, S.Z. Josefowicz, A. Arvey, P.M. Treuting, and A.Y. Rudensky Extrathymic generation of regulatory T cells in placental mammals mitigates maternal-fetal conflict Cell 150 1 2012 29 38
145. X.O. Yang, R. Nurieva, G.J. Martinez, and et al. Molecular antagonism and plasticity of regulatory and inflammatory T cell programs Immunity 29 1 2008 44 56
146. L. Zhou, J.E. Lopes, M.M. Chong, and et al. TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function Nature 453 7192 2008 236 240
147. K. Ichiyama, H. Yoshida, Y. Wakabayashi, and et al. Foxp3 inhibits RORgammat-mediated IL-17A mRNA transcription through direct interaction with RORgammat J Biol Chem 283 25 2008 17003 17008
148. Z. Chen, J. Barbi, S. Bu, and et al. The ubiquitin ligase Stub1 negatively modulates regulatory T cell suppressive activity by promoting degradation of the transcription factor Foxp3 Immunity 39 2 2013 272 285
149. M. Noack, and P. Miossec Th17 and regulatory T cell balance in autoimmune and inflammatory diseases Autoimmun Rev 13 6 2014 668 677
150. F. Osorio, S. LeibundGut-Landmann, M. Lochner, and et al. DC activated via dectin-1 convert Treg into IL-17 producers Eur J Immunol 38 12 2008 3274 3281
151. L. Li, J. Kim, and V.A. Boussiotis IL-1beta-mediated signals preferentially drive conversion of regulatory T cells but not conventional T cells into IL-17-producing cells J Immunol 185 7 2010 4148 4153
152. L. Li, N. Patsoukis, V. Petkova, and V.A. Boussiotis Runx1 and Runx3 are involved in the generation and function of highly suppressive IL-17-producing T regulatory cells PLoS One 7 9 2012 e45115
153. M. Esposito, F. Ruffini, A. Bergami, and et al. IL-17- and IFN-gamma-secreting Foxp3 + T cells infiltrate the target tissue in experimental autoimmunity J Immunol 185 12 2010 7467 7473
154. D.M. Tartar, A.M. VanMorlan, X. Wan, and et al. FoxP3+RORgammat + T helper intermediates display suppressive function against autoimmune diabetes J Immunol 184 7 2010 3377 3385
155. N. Komatsu, K. Okamoto, S. Sawa, and et al. Pathogenic conversion of Foxp3 + T cells into TH17 cells in autoimmune arthritis Nat Med 20 1 2014 62 68
156. S. Floess, J. Freyer, C. Siewert, and et al. Epigenetic control of the foxp3 locus in regulatory T cells PLoS Biol 5 2 2007 e38
157. T. Miyao, S. Floess, R. Setoguchi, and et al. Plasticity of Foxp3(+) T cells reflects promiscuous Foxp3 expression in conventional T cells but not reprogramming of regulatory T cells Immunity 36 2 2012 262 275
158. N. Ohkura, M. Hamaguchi, H. Morikawa, and et al. T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development Immunity 37 5 2012 785 799
159. J.K. Polansky, K. Kretschmer, J. Freyer, and et al. DNA methylation controls Foxp3 gene expression Eur J Immunol 38 6 2008 1654 1663
160. M. Miyara, Y. Yoshioka, A. Kitoh, and et al. Functional delineation and differentiation dynamics of human CD4 + T cells expressing the FoxP3 transcription factor Immunity 30 6 2009 899 911
161. J. Huehn, and A. Hamann Homing to suppress: address codes for Treg migration Trends Immunol 26 12 2005 632 636
162. A. Liston, and D.H. Gray Homeostatic control of regulatory T cell diversity Nat Rev Immunol 14 3 2014 154 165
163. M. Feuerer, J.A. Hill, K. Kretschmer, H. von Boehmer, D. Mathis, and C. Benoist Genomic definition of multiple ex vivo regulatory T cell subphenotypes Proc Natl Acad Sci USA 107 13 2010 5919 5924
164. M. Delacher, L. Schreiber, D.M. Richards, C. Farah, M. Feuerer, and J. Huehn Transcriptional control of regulatory T cells Curr Top Microbiol Immunol 381 2014 83 124
165. M.A. Koch, G. Tucker-Heard, N.R. Perdue, J.R. Killebrew, K.B. Urdahl, and D.J. Campbell The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation Nat Immunol 10 6 2009 595 602
166. Y. Wang, M.A. Su, and Y.Y. Wan An essential role of the transcription factor GATA-3 for the function of regulatory T cells Immunity 35 3 2011 337 348
167. E.A. Wohlfert, J.R. Grainger, N. Bouladoux, and et al. GATA3 controls Foxp3(+) regulatory T cell fate during inflammation in mice J Clin Invest 121 11 2011 4503 4515
168. E. Cretney, A. Kallies, and S.L. Nutt Differentiation and function of Foxp3(+) effector regulatory T cells Trends Immunol 34 2 2013 74 80
169. E. Cretney, A. Xin, W. Shi, and et al. The transcription factors Blimp-1 and IRF4 jointly control the differentiation and function of effector regulatory T cells Nat Immunol 12 4 2011 304 311
170. M. Ayyoub, F. Deknuydt, I. Raimbaud, and et al. Human memory FOXP3 + Tregs secrete IL-17 ex vivo and constitutively express the T(H)17 lineage-specific transcription factor RORgamma t Proc Natl Acad Sci USA 106 21 2009 8635 8640
171. G. Beriou, C.M. Costantino, C.W. Ashley, and et al. IL-17-producing human peripheral regulatory T cells retain suppressive function Blood 113 18 2009 4240 4249
172. K.S. Voo, Y.H. Wang, F.R. Santori, and et al. Identification of IL-17-producing FOXP3 + regulatory T cells in humans Proc Natl Acad Sci U S A 106 12 2009 4793 4798
173. I. Kryczek, K. Wu, E. Zhao, and et al. IL-17 + regulatory T cells in the microenvironments of chronic inflammation and cancer J Immunol 186 7 2011 4388 4395
174. M.H. Nyirenda, L. Sanvito, P.J. Darlington, and et al. TLR2 stimulation drives human naive and effector regulatory T cells into a Th17-like phenotype with reduced suppressive function J Immunol 187 5 2011 2278 2290
175. M.H. Nyirenda, E. Morandi, U. Vinkemeier, and et al. TLR2 stimulation regulates the balance between regulatory T cell and Th17 function: a novel mechanism of reduced regulatory T cell function in multiple sclerosis J Immunol 194 12 2015 5761 5774
176. H.J. Koenen, R.L. Smeets, P.M. Vink, E. van Rijssen, A.M. Boots, and I. Joosten Human CD25highFoxp3pos regulatory T cells differentiate into IL-17-producing cells Blood 112 6 2008 2340 2352
177. D. Valmori, C. Raffin, I. Raimbaud, and M. Ayyoub Human RORgammat + TH17 cells preferentially differentiate from naive FOXP3+Treg in the presence of lineage-specific polarizing factors Proc Natl Acad Sci USA 107 45 2010 19402 19407
178. M.J. Benson, K. Pino-Lagos, M. Rosemblatt, and R.J. Noelle All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation J Exp Med 204 8 2007 1765 1774
179. J.L. Coombes, K.R. Siddiqui, C.V. Arancibia-Carcamo, and et al. A functionally specialized population of mucosal CD103 + DCs induces Foxp3 + regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism J Exp Med 204 8 2007 1757 1764
180. C.M. Sun, J.A. Hall, R.B. Blank, and et al. Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid J Exp Med 204 8 2007 1775 1785
181. N. Arpaia, C. Campbell, X. Fan, and et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation Nature 504 7480 2013 451 455
182. Y. Furusawa, Y. Obata, S. Fukuda, and et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells Nature 504 7480 2013 446 450
183. P.M. Smith, M.R. Howitt, N. Panikov, and et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis Science 341 6145 2013 569 573
184. R. Basu, S.K. Whitley, S. Bhaumik, and et al. IL-1 signaling modulates activation of STAT transcription factors to antagonize retinoic acid signaling and control the TH17 cell-iTreg cell balance Nat Immunol 16 3 2015 286 295
185. A. Chaudhry, R.M. Samstein, P. Treuting, and et al. Interleukin-10 signaling in regulatory T cells is required for suppression of Th17 cell-mediated inflammation Immunity 34 4 2011 566 578
186. S. Huber, N. Gagliani, E. Esplugues, and et al. Th17 cells express interleukin-10 receptor and are controlled by Foxp3(-) and Foxp3 + regulatory CD4 + T cells in an interleukin-10-dependent manner Immunity 34 4 2011 554 565
187. N. Joller, E. Lozano, P.R. Burkett, and et al. Treg cells expressing the coinhibitory molecule TIGIT selectively inhibit proinflammatory Th1 and Th17 cell responses Immunity 40 4 2014 569 581
188. X. Yu, K. Harden, L.C. Gonzalez, and et al. The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells Nat Immunol 10 1 2009 48 57
189. Y. Chen, C.J. Haines, I. Gutcher, and et al. Foxp3(+) regulatory T cells promote T helper 17 cell development in vivo through regulation of interleukin-2 Immunity 34 3 2011 409 421
190. B. Leon, J.E. Bradley, F.E. Lund, T.D. Randall, and A. Ballesteros-Tato FoxP3 + regulatory T cells promote influenza-specific Tfh responses by controlling IL-2 availability Nat Commun 5 2014 3495
191. A. Izcue, J.L. Coombes, and F. Powrie Regulatory lymphocytes and intestinal inflammation Annu Rev Immunol 27 2009 313 338
192. T. Sujino, T. Kanai, Y. Ono, and et al. Regulatory T cells suppress development of colitis, blocking differentiation of T-helper 17 into alternative T-helper 1 cells Gastroenterology 141 3 2011 1014 1023
193. T.S. Davidson, R.J. DiPaolo, J. Andersson, and E.M. Shevach Cutting edge: IL-2 is essential for TGF-beta-mediated induction of Foxp3 + T regulatory cells J Immunol 178 7 2007 4022 4026
194. S. Sakaguchi, T. Yamaguchi, T. Nomura, and M. Ono Regulatory T cells and immune tolerance Cell 133 5 2008 775 787
195. E.M. Shevach Application of IL-2 therapy to target T regulatory cell function Trends Immunol 33 12 2012 626 632
196. A. Laurence, C.M. Tato, T.S. Davidson, and et al. Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation Immunity 26 3 2007 371 381
197. J.M. Moore-Connors, R. Fraser, S.A. Halperin, and J. Wang CD4(+)CD25(+)Foxp3(+) regulatory T cells promote Th17 responses and genital tract inflammation upon intracellular Chlamydia muridarum infection J Immunol 191 6 2013 3430 3439
198. P. Pandiyan, H.R. Conti, L. Zheng, and et al. CD4(+)CD25(+)Foxp3(+) regulatory T cells promote Th17 cells in vitro and enhance host resistance in mouse Candida albicans Th17 cell infection model Immunity 34 3 2011 422 434
199. Z. Wang, C. Friedrich, S.C. Hagemann, and et al. Regulatory T cells promote a protective Th17-associated immune response to intestinal bacterial infection with C. rodentium Mucosal Immunol 7 6 2014 1290 1301
200. A. Amadi-Obi, C.R. Yu, X. Liu, and et al. TH17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1 Nat Med 13 6 2007 711 718
201. G. Gasteiger, S. Hemmers, P.D. Bos, J.C. Sun, and A.Y. Rudensky IL-2-dependent adaptive control of NK cell homeostasis J Exp Med 210 6 2013 1179 1187
202. G. Gasteiger, S. Hemmers, M.A. Firth, and et al. IL-2-dependent tuning of NK cell sensitivity for target cells is controlled by regulatory T cells J Exp Med 210 6 2013 1167 1178
203. J. Barbi, D. Pardoll, and F. Pan Metabolic control of the Treg/Th17 axis Immunol Rev 252 1 2013 52 77