The dichotomous nature of T helper 17 cells

Nature Reviews Immunology

Volumn 17, Issue 9, 2017, Pages 535-544

  Stockinger, Brigitta ^a   Omenetti, Sara ^a  

^a THE FRANCIS CRICK INSTITUTE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

HUMAN; INFLAMMATION; INFLAMMATORY DISEASE; INTESTINE MUCOSA PERMEABILITY; LYMPHOCYTE FUNCTION; NONHUMAN; PATHOGENESIS; PERMEABILITY BARRIER; PRIORITY JOURNAL; REVIEW; TH17 CELL; TRANSCRIPTOMICS; CELL PLASTICITY; GENE EXPRESSION PROFILING; IMMUNOLOGY; INFLAMMATORY BOWEL DISEASE; INTESTINE; INTESTINE FLORA; METABOLISM; MICROBIOLOGY; MUCOSAL IMMUNITY; PERMEABILITY;

CELL PLASTICITY; GASTROINTESTINAL MICROBIOME; GENE EXPRESSION PROFILING; HUMANS; IMMUNITY, MUCOSAL; INFLAMMATION; INFLAMMATORY BOWEL DISEASES; INTESTINES; PERMEABILITY; TH17 CELLS;

EID: 85028351441     PISSN: 14741733     EISSN: 14741741     Source Type: Journal    
DOI: 10.1038/nri.2017.50     Document Type: Review

References (98)

1. Hernandez-Santos, N., et al. Th17 cells confer long-term adaptive immunity to oral mucosal Candida albicans infections. Mucosal Immunol. 6, 900-910 (2013
2. Chen, K., & Kolls, J. K. T cell-mediated host immune defenses in the lung. Annu. Rev. Immunol. 31, 605-633 (2013
3. Yosef, N., et al. Dynamic regulatory network controlling TH17 cell differentiation. Nature 496, 461-468 (2013
4. Ciofani, M., et al. A validated regulatory network for Th17 cell specification. Cell 151, 289-303 (2012
5. Lee, Y., et al. Induction and molecular signature of pathogenic TH17 cells. Nat. Immunol. 13, 991-999 (2012
6. Gaublomme, J. T., et al. Single-cell genomics unveils critical regulators of Th17 cell pathogenicity. Cell 163, 1400-1412 (2015
7. Hirota, K., et al. Fate mapping of IL 17 producing T cells in inflammatory responses. Nat. Immunol. 12, 255-263 (2011
8. Tuomela, S., et al. Comparative analysis of human and mouse transcriptomes of Th17 cell priming. Oncotarget 7, 13416-13428 (2016
9. McGeachy, M. J., et al. TGF-β and IL 6 drive the production of IL 17 and IL 10 by T cells and restrain TH-17 cell-mediated pathology. Nat. Immunol. 8, 1390-1397 (2007
10. Ghoreschi, K., et al. Generation of pathogenic TH17 cells in the absence of TGF-β signalling. Nature 467, 967-971 (2010
11. Veldhoen, M., Hocking, R. J., Flavell, R. A., & Stockinger, B. Signals mediated by transforming growth factor-β initiate autoimmune encephalomyelitis, but chronic inflammation is needed to sustain disease. Nat. Immunol. 7, 1151-1156 (2006
12. Heink, S., et al. Trans-presentation of IL 6 by dendritic cells is required for the priming of pathogenic TH17 cells. Nat. Immunol. 18, 74-85 (2017
13. Wang, C., et al. CD5L/AIM regulates lipid biosynthesis and restrains Th17 cell pathogenicity. Cell 163, 1413-1427 (2015
14. Langrish, C. L., et al. IL 23 drives a pathogenic T cell population that induces autoimmune inflammation. J. Exp. Med. 201, 233-240 (2005
15. Meyer Zu Horste, G., et al. RBPJ controls development of pathogenic Th17 cells by regulating IL 23 receptor expression. Cell Rep. 16, 392-404 (2016
16. Kishi, Y., et al. Protein C receptor (PROCR) is a negative regulator of Th17 pathogenicity. J. Exp. Med. 213, 2489-2501 (2016
17. Ichiyama, K., et al. The microRNA 183 96 182 cluster promotes T helper 17 cell pathogenicity by negatively regulating transcription factor Foxo1 expression. Immunity 44, 1284-1298 (2016
18. Du, C., et al. MicroRNA miR 326 regulates TH 17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat. Immunol. 10, 1252-1259 (2009
19. Sutton, C., Brereton, C., Keogh, B., Mills, K. H., & Lavelle, E. C. A crucial role for interleukin (IL)-1 in the induction of IL 17 producing T cells that mediate autoimmune encephalomyelitis. J. Exp. Med. 203, 1685-1691 (2006
20. Murugaiyan, G., et al. MicroRNA 21 promotes Th17 differentiation and mediates experimental autoimmune encephalomyelitis. J. Clin. Invest. 125, 1069-1080 (2015
21. Mycko, M. P., et al. MicroRNA 301a regulation of a T helper 17 immune response controls autoimmune demyelination. Proc. Natl Acad. Sci. USA 109, E1248-E1257 (2012
22. Escobar, T. M., et al. miR 155 activates cytokine gene expression in Th17 cells by regulating the DNA-binding protein Jarid2 to relieve Polycomb-mediated repression. Immunity 40, 865-879 (2014
23. Sandhu, S. K., et al. miR 155 targets histone deacetylase 4 (HDAC4) and impairs transcriptional activity of B cell lymphoma 6 (BCL6) in the E-miR 155 transgenic mouse model. Proc. Natl Acad. Sci. USA 109, 20047-20052 (2012
24. Veldhoen, M., et al. The aryl hydrocarbon receptor links TH17 cell-mediated autoimmunity to environmental toxins. Nature 453, 106-109 (2008
25. Huang, W., et al. DDX5 and its associated lncRNA Rmrp modulate TH17 cell effector functions. Nature 528, 517-522 (2015
26. Kofler, D. M., et al. Decreased RORC-dependent silencing of prostaglandin receptor EP2 induces autoimmune Th17 cells. J. Clin. Invest. 124, 2513-2522 (2014
27. Zielinski, C. E., et al. Pathogen-induced human TH17 cells produce IFN-κ. or IL 10 and are regulated by IL 1β. Nature 484, 514-518 (2012
28. Becattini, S., et al. T cell immunity. Functional heterogeneity of human memory CD4+ T cell clones primed by pathogens or vaccines. Science 347, 400-406 (2015
29. Harbour, S. N., Maynard, C. L., Zindl, C. L., Schoeb, T. R., & Weaver, C. T. Th17 cells give rise to Th1 cells that are required for the pathogenesis of colitis. Proc. Natl Acad. Sci. USA 112, 7061-7066 (2015
30. Morrison, P. J., et al. Th17 cell plasticity in Helicobacter hepaticus-induced intestinal inflammation. Mucosal Immunol. 6, 1143-1156 (2013
31. Ahlfors, H., et al. IL 22 fate reporter reveals origin and control of IL 22 production in homeostasis and infection. J. Immunol. 193, 4602-4613 (2014
32. Jostins, L., et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491, 119-124 (2012
33. Krebs, C. F., et al. Plasticity of Th17 cells in autoimmune kidney diseases. J. Immunol. 197, 449-457 (2016
34. Krebs, C. F., et al. Autoimmune renal disease is exacerbated by S1P receptor 1 dependent intestinal Th17 cell migration to the kidney. Immunity 45, 1078-1092 (2016
35. Jain, R., et al. Interleukin 23 induced transcription factor Blimp 1 promotes pathogenicity of T helper 17 cells. Immunity 44, 131-142 (2016
36. Krausgruber, T., et al. T Bet is a key modulator of IL 23 driven pathogenic CD4+ T cell responses in the intestine. Nat. Commun. 7, 11627 (2016
37. Ahern, P. P., Izcue, A., Maloy, K. J., & Powrie, F. The interleukin 23 axis in intestinal inflammation. Immunol. Rev. 226, 147-159 (2008
38. Duerr, R. H., et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314, 1461-1463 (2006
39. Hirota, K., et al. Plasticity of Th17 cells in Peyers patches is responsible for the induction of T cell-dependent IgA responses. Nat. Immunol. 14, 372-379 (2013
40. Gagliani, N., et al. Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation. Nature 523, 221-225 (2015
41. Cua, D. J., & Tato, C. M. Innate IL 17 producing cells: the sentinels of the immune system. Nat. Rev. Immunol. 10, 479-489 (2010
42. Conti, H. R., et al. Oral-resident natural Th17 cells and ?d T cells control opportunistic Candida albicans infections. J. Exp. Med. 211, 2075-2084 (2014
43. Puel, A., et al. Inborn errors of human IL 17 immunity underlie chronic mucocutaneous candidiasis. Curr. Opin. Allergy Clin. Immunol. 12, 616-622 (2012
44. Busbee, P. B., Rouse, M., Nagarkatti, M., & Nagarkatti, P. S. Use of natural AhR ligands as potential therapeutic modalities against inflammatory disorders. Nutr. Rev. 71, 353-369 (2013
45. Nguyen, L. P., & Bradfield, C. A. The search for endogenous activators of the aryl hydrocarbon receptor. Chem. Res. Toxicol. 21, 102-116 (2008
46. Zelante, T., et al. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin 22. Immunity 39, 372-385 (2013
47. Stockinger, B., Di Meglio, P., Gialitakis, M., & Duarte, J. H. The aryl hydrocarbon receptor: multitasking in the immune system. Annu. Rev. Immunol. 32, 403-432 (2014
48. Endo, Y., et al. Obesity drives Th17 cell differentiation by inducing the lipid metabolic kinase, ACC1. Cell Rep. 12, 1042-1055 (2015
49. Berod, L., et al. De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells. Nat. Med. 20, 1327-1333 (2014
50. Garidou, L., et al. The gut microbiota regulates intestinal CD4 T cells expressing RORγt and controls metabolic disease. Cell Metab. 22, 100-112 (2015
51. Kleinewietfeld, M., et al. Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature 496, 518-522 (2013
52. Wu, C., et al. Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1. Nature 496, 513-517 (2013
53. Yu, X., et al. TH17 cell differentiation is regulated by the circadian clock. Science 342, 727-730 (2013
54. Farez, M. F., et al. Melatonin contributes to the seasonality of multiple sclerosis relapses. Cell 162, 1338-1352 (2015
55. Cummins, E. P., & Crean, D. Hypoxia and inflammatory bowel disease. Microbes Infect. 19, 210-221 (2017
56. Glover, L. E., Lee, J. S., & Colgan, S. P. Oxygen metabolism and barrier regulation in the intestinal mucosa. J. Clin. Invest. 126, 3680-3688 (2016
57. Dang, E. V., et al. Control of TH17/Treg balance by hypoxia-inducible factor 1. Cell 146, 772-784 (2011
58. Shi, L. Z., et al. HIF1a dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J. Exp. Med. 208, 1367-1376 (2011
59. Wang, H., et al. Negative regulation of Hif1a expression and TH17 differentiation by the hypoxia-regulated microRNA miR 210. Nat. Immunol. 15, 393-401 (2014
60. Kelly, C. J., et al. Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial HIF augments tissue barrier function. Cell Host Microbe 17, 662-671 (2015
61. Ivanov, I. I., et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139, 485-498 (2009
62. Prakash, T., et al. Complete genome sequences of rat and mouse segmented filamentous bacteria, a potent inducer of Th17 cell differentiation. Cell Host Microbe 10, 273-284 (2011
63. Gaboriau-Routhiau, V., et al. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 31, 677-689 (2009
64. Schnupf, P., Gaboriau-Routhiau, V., & Cerf-Bensussan, N. Host interactions with segmented filamentous bacteria: an unusual trade-off that drives the post-natal maturation of the gut immune system. Semin. Immunol. 25, 342-351 (2013
65. Kumar, P., et al. Intestinal interleukin 17 receptor signaling mediates reciprocal control of the gut microbiota and autoimmune inflammation. Immunity 44, 659-671 (2016
66. Yang, Y., et al. Focused specificity of intestinal TH17 cells towards commensal bacterial antigens. Nature 510, 152-156 (2014
67. Panea, C., et al. Intestinal monocyte-derived macrophages control commensal-specific Th17 responses. Cell Rep. 12, 1314-1324 (2015
68. Goto, Y., et al. Segmented filamentous bacteria antigens presented by intestinal dendritic cells drive mucosal Th17 cell differentiation. Immunity 40, 594-607 (2014
69. Sano, T., et al. An IL 23R/IL 22 circuit regulates epithelial serum amyloid A to promote local effector Th17 responses. Cell 163, 381-393 (2015
70. Atarashi, K., et al. Th17 cell induction by adhesion of microbes to intestinal epithelial cells. Cell 163, 367-380 (2015
71. Yin, Y., et al. Comparative analysis of the distribution of segmented filamentous bacteria in humans, mice and chickens. ISME J. 7, 615-621 (2013
72. Torchinsky, M. B., Garaude, J., Martin, A. P., & Blander, J. M. Innate immune recognition of infected apoptotic cells directs TH17 cell differentiation. Nature 458, 78-82 (2009
73. Sansonetti, P. J. To be or not to be a pathogen: that is the mucosally relevant question. Mucosal Immunol. 4, 8-14 (2011
74. Stepankova, R., et al. Segmented filamentous bacteria in a defined bacterial cocktail induce intestinal inflammation in SCID mice reconstituted with CD45RBhigh CD4+ T cells. Inflamm. Bowel Dis. 13, 1202-1211 (2007
75. Wu, H. J., et al. Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 32, 815-827 (2010
76. Lee, Y. K., Menezes, J. S., Umesaki, Y., & Mazmanian, S. K. Proinflammatory T cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc. Natl Acad. Sci. USA 108 (Suppl. 1), 4615-4622 (2011
77. Berer, K., et al. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature 479, 538-541 (2011
78. Belkaid, Y., & Hand, T. W. Role of the microbiota in immunity and inflammation. Cell 157, 121-141 (2014
79. Kusu, T., et al. Ecto-nucleoside triphosphate diphosphohydrolase 7 controls Th17 cell responses through regulation of luminal ATP in the small intestine. J. Immunol. 190, 774-783 (2013
80. Kolls, J. K., McCray, P. B. Jr & Chan, Y. R. Cytokine-mediated regulation of antimicrobial proteins. Nat. Rev. Immunol. 8, 829-835 (2008
81. Kinugasa, T., Sakaguchi, T., Gu, X., & Reinecker, H. C. Claudins regulate the intestinal barrier in response to immune mediators. Gastroenterology 118, 1001-1011 (2000
82. Lee, J. S., et al. Interleukin 23 independent IL 17 production regulates intestinal epithelial permeability. Immunity 43, 727-738 (2015
83. Zheng, Y., et al. Interleukin 22 mediates early host defense against attaching and effacing bacterial pathogens. Nat. Med. 14, 282-289 (2008
84. Birchenough, G. M., Johansson, M. E., Gustafsson, J. K., Bergstrom, J. H., & Hansson, G. C. New developments in goblet cell mucus secretion and function. Mucosal Immunol. 8, 712-719 (2015
85. Basu, R., et al. Th22 cells are an important source of IL 22 for host protection against enteropathogenic bacteria. Immunity 37, 1061-1075 (2012
86. Behnsen, J., et al. The cytokine IL 22 promotes pathogen colonization by suppressing related commensal bacteria. Immunity 40, 262-273 (2014
87. Patel, D. D., & Kuchroo, V. K. Th17 cell pathway in human immunity: lessons from genetics and therapeutic interventions. Immunity 43, 1040-1051 (2015
88. Sherlock, J. P., et al. IL 23 induces spondyloarthropathy by acting on ROR-κt+CD3+CD4-CD8-entheseal resident T cells. Nat. Med. 18, 1069-1076 (2012
89. Hueber, W., et al. Secukinumab, a human anti IL 17A monoclonal antibody, for moderate to severe Crohns disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut 61, 1693-1700 (2012
90. Colombel, J. F., Sendid, B., Jouault, T., & Poulain, D. Secukinumab failure in Crohns disease: the yeast connection? Gut 62, 800-801 (2013
91. Puel, A., et al. Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin 17 immunity. Science 332, 65-68 (2011
92. 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
93. Feagan, B. G., et al. Ustekinumab as induction and maintenance therapy for Crohns disease. N. Engl. J. Med. 375, 1946-1960 (2016
94. Xiao, S., et al. Small-molecule RORγt antagonists inhibit T helper 17 cell transcriptional network by divergent mechanisms. Immunity 40, 477-489 (2014
95. Withers, D. R., et al. Transient inhibition of ROR-κt therapeutically limits intestinal inflammation by reducing TH17 cells and preserving group 3 innate lymphoid cells. Nat. Med. 22, 319-323 (2016
96. Lim, H. W., et al. SIRT1 deacetylates RORγt and enhances Th17 cell generation. J. Exp. Med. 212, 607-617 (2015
97. Ueda, E., et al. High incidence of T cell lymphomas in mice deficient in the retinoid-related orphan receptor RORγ. Cancer Res. 62, 901-909 (2002
98. Conti, H. R., & Gaffen, S. L. IL-17-mediated immunity to the opportunistic fungal pathogen Candida albicans. J. Immunol. 195, 780-788 (2015