The Th17 family: Flexibility follows function

Immunological Reviews

Volumn 252, Issue 1, 2013, Pages 89-103

  Basu, Rajatava ^a   Hatton, Robin D ^a   Weaver, Casey T ^a  

^a University of Alabama at Birmingham   (United States)

Author keywords

Cytokines; Plasticity; T cell development; Th1 cells; Th17 cells; Th22 cells; Treg cells

Indexed keywords

ALPHA INTERFERON; BETA ACTIN; BETA INTERFERON; GAMMA INTERFERON; IMMUNOGLOBULIN G ANTIBODY; INTERLEUKIN 13; INTERLEUKIN 17; INTERLEUKIN 4; INTERLEUKIN 5; STAT4 PROTEIN; STAT5 PROTEIN; SUPPRESSOR OF CYTOKINE SIGNALING 3; TRANSCRIPTION FACTOR FOXP3; TRANSCRIPTION FACTOR GATA 3; TRANSCRIPTION FACTOR NFAT;

ADAPTIVE IMMUNITY; ALLERGIC ENCEPHALOMYELITIS; ANTIGEN PRESENTATION; ARTICLE; BIOTRANSFORMATION; BONE MARROW CELL; CD4+ T LYMPHOCYTE; CYTOKINE PRODUCTION; EFFECTOR CELL; EPIGENETICS; GENE LOCUS; GENETIC ASSOCIATION; HOMEOSTASIS; HOST RESISTANCE; HUMAN; IMMUNE RESPONSE; IMMUNOCOMPETENT CELL; IMMUNOREGULATION; INHIBITION KINETICS; INSULIN DEPENDENT DIABETES MELLITUS; LYMPHOCYTE DIFFERENTIATION; LYMPHOCYTE FUNCTION; MELANOMA; MICROENVIRONMENT; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; PATHOGENESIS; PHENOTYPE; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN INTERACTION; PROTEIN STABILITY; PSORIASIS; REGULATORY T LYMPHOCYTE; RHEUMATOID ARTHRITIS; SIGNAL TRANSDUCTION; TH1 CELL; TH17 CELL; TH2 CELL; UPREGULATION;

CELL DIFFERENTIATION; FORKHEAD TRANSCRIPTION FACTORS; GENE EXPRESSION REGULATION; HOMEOSTASIS; HUMANS; INTERFERON-GAMMA; INTERLEUKIN-12; INTERLEUKIN-17; NUCLEAR RECEPTOR SUBFAMILY 1, GROUP F, MEMBER 3; SIGNAL TRANSDUCTION; T-LYMPHOCYTES, REGULATORY; TH1 CELLS; TH17 CELLS; TRANSFORMING GROWTH FACTOR BETA;

EID: 84873626771     PISSN: 01052896     EISSN: 1600065X     Source Type: Journal    
DOI: 10.1111/imr.12035     Document Type: Article

References (104)

1. Crotty S. Follicular helper CD4 T cells (TFH). Annu Rev Immunol 2011;29:621-663.
2. Lee YK, Mukasa R, Hatton RD, Weaver CT. Developmental plasticity of Th17 and Treg cells. Curr Opin Immunol 2009;21:274-280.
3. Murphy KM, Stockinger B. Effector T cell plasticity: flexibility in the face of changing circumstances. Nat Immunol 2010;11:674-680.
4. Mitsdoerffer M, et al. Proinflammatory T helper type 17 cells are effective B-cell helpers. Proc Natl Acad Sci U S A 2010;107:14292-14297.
5. Cong Y, Feng T, Fujihashi K, Schoeb TR, Elson CO. A dominant, coordinated T regulatory cell-IgA response to the intestinal microbiota. Proc Natl Acad Sci USA 2009;106:19256-19261.
6. Murphy KM, Reiner SL. The lineage decisions of helper T cells. Nat Rev Immunol 2002;2:933-944.
7. Harrington LE, 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 2005;6:1123-1132.
8. Stumhofer JS, et al. Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system. Nat Immunol 2006;7:937-945.
9. H17 and regulatory T cells. Nature 2006;441:235-238.
10. H17 lineage. Nature 2006;441:231-234.
11. Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B. TGFβ in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 2006;24:179-189.
12. Maynard CL, Elson CO, Hatton RD, Weaver CT. Reciprocal interactions of the intestinal microbiota and immune system. Nature 2012;489:231-241.
13. Li MO, Wan YY, Sanjabi S, Robertson AK, Flavell RA. Transforming growth factor-β regulation of immune responses. Annu Rev Immunol 2006;24:99-146.
14. Gorelik L, Flavell RA. Abrogation of TGFβ signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease. Immunity 2000;12:171-181.
15. Ivanov II, et al. The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 2006;126:1121-1133.
16. Du J, Huang C, Zhou B, Ziegler SF. Isoform-specific inhibition of ROR α-mediated transcriptional activation by human FOXP3. J Immunol 2008;180:4785-4792.
17. H17 cell differentiation by antagonizing RORgammat function. Nature 2008;453:236-240.
18. Ichiyama K, et al. Foxp3 inhibits RORγt-mediated IL-17A mRNA transcription through direct interaction with RORγt. J Biol Chem 2008;283:17003-17008.
19. Yang XO, et al. Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity 2008;29:44-56.
20. Hoechst B, Gamrekelashvili J, Manns MP, Greten TF, Korangy F. Plasticity of human Th17 cells and iTregs is orchestrated by different subsets of myeloid cells. Blood 2011;117:6532-6541.
21. pos regulatory T cells differentiate into IL-17-producing cells. Blood 2008;112:2340-2352.
22. Zheng Y, Josefowicz S, Chaudhry A, Peng XP, Forbush K, Rudensky AY. Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory. T-Cell Fate 2010;463:808-812.
23. + regulatory T cells via a TGF-β and retinoic acid-dependent mechanism. J Exp Med 2007;204:1757-1764.
24. H17 and regulatory T cell differentiation mediated by retinoic acid. Science 2007;317:256-260.
25. Schambach F, Schupp M, Lazar MA, Reiner SL. Activation of retinoic acid receptor-alpha favours regulatory T cell induction at the expense of IL-17-secreting T helper cell differentiation. Eur J Immunol 2007;37:2396-2399.
26. Elias KM, et al. Retinoic acid inhibits Th17 polarization and enhances FoxP3 expression through a Stat-3/Stat-5 independent signaling pathway. Blood 2008;111:1013-1020.
27. Laurence A, et al. Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity 2007;26:371-381.
28. Yang XP, et al. Opposing regulation of the locus encoding IL-17 through direct, reciprocal actions of STAT3 and STAT5. Nat Immunol 2011;12:247-254.
29. Park H, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 2005;6:1133-1141.
30. Lee YK, et al. Late developmental plasticity in the T helper 17 lineage. Immunity 2009;30:92-107.
31. Annunziato F, et al. Phenotypic and functional features of human Th17 cells. J Exp Med 2007;204:1849-1861.
32. Lexberg MH, et al. Th memory for interleukin-17 expression is stable in vivo. Eur J Immunol 2008;38:2654-2664.
33. Cosmi L, Liotta F, Maggi E, Romagnani S, Annunziato F. Th17 cells: new players in asthma pathogenesis. Allergy 2011;66:989-998.
34. + T cells that produce both IL-17A and IL-4. J Allergy Clin Immunol 2010;125:222-230. e221-224.
35. Khor B, Gardet A, Xavier RJ. Genetics and pathogenesis of inflammatory bowel disease. Nature 2011;474:307-317.
36. Hirota K, et al. Fate mapping of IL-17-producing T cells in inflammatory responses. Nat Immunol 2011;12:255-263.
37. Cua DJ, et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 2003;421:744-748.
38. Murphy CA, et al. Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med 2003;198:1951-1957.
39. Ahern PP, et al. Interleukin-23 drives intestinal inflammation through direct activity on T cells. Immunity 2010;33:279-288.
40. Bending D, et al. Highly purified Th17 cells from BDC2.5NOD mice convert into Th1-like cells in NOD/SCID recipient mice. J Clin Invest 2009;119:565-572.
41. Muranski P, et al. Tumor-specific Th17-polarized cells eradicate large established melanoma. Blood 2008;112:362-373.
42. Martin-Orozco N, et al. T helper 17 cells promote cytotoxic T cell activation in tumor immunity. Immunity 2009;31:787-798.
43. Muranski P, et al. Th17 cells are long lived and retain a stem cell-like molecular signature. Immunity 2011;35:972-985.
44. Luckey CJ, Weaver CT. Stem-cell-like qualities of immune memory; CD4(+) T cells join the party. Cell Stem Cell 2012;10:107-108.
45. Wilson NJ, et al. Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol 2007;8:950-957.
46. Acosta-Rodriguez EV, Napolitani G, Lanzavecchia A, Sallusto F. Interleukins 1beta and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol 2007;8:942-949.
47. Manel N, Unutmaz D, Littman DR. The differentiation of human TH-17 cells requires transforming growth factor-beta and induction of the nuclear receptor RORγt. Nat Immunol 2008;9:641-649.
48. H-17 responses. Nat Immunol 2008;9:650-657.
49. H17 cells. Nature 2008;454:350-352.
50. H17 cells in the absence of TGF-β signalling. Nature 2010;467:967-971.
51. Wakefield LM, et al. Transforming growth factor-beta1 circulates in normal human plasma and is unchanged in advanced metastatic breast cancer. Clin Cancer Res 1995;1:129-136.
52. Gutcher I, Donkor MK, Ma Q, Rudensky AY, Flavell RA, Li MO. Autocrine transforming growth factor-β1 promotes in vivo Th17 cell differentiation. Immunity 2011;34:396-408.
53. Veldhoen M, Hocking RJ, Flavell RA, Stockinger B. Signals mediated by transforming growth factor-β initiate autoimmune encephalomyelitis, but chronic inflammation is needed to sustain disease. Nat Immunol 2006;7:1151-1156.
54. Veldhoen M, Stockinger B. TGFβ1, a 'Jack of all trades': the link with pro-inflammatory IL-17-producing T cells. Trends Immunol 2006;27:358-361.
55. H-17 cell-mediated pathology. Nat Immunol 2007;8:1390-1397.
56. H17 cells. Nat Immunol 2012;13:991-999.
57. Liang SC, et al. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 2006;203:2271-2279.
58. H17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 2007;445:648-651.
59. Aujla SJ, et al. IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nat Med 2008;14:275-281.
60. Zheng Y, et al. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med 2008;14:282-289.
61. Gurney AL. IL-22, a Th1 cytokine that targets the pancreas and select other peripheral tissues. Int Immunopharmacol 2004;4:669-677.
62. Duhen T, Geiger R, Jarrossay D, Lanzavecchia A, Sallusto F. Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells. Nat Immunol 2009;10:857-863.
63. H17 cells. Nat Immunol 2011;12:1238-1245.
64. Eyerich S, Eyerich K, Cavani A, Schmidt-Weber C. IL-17 and IL-22: siblings, not twins. Trends Immunol 2010;31:354-361.
65. Eyerich S, et al. Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling. J Clin Invest 2009;119:3573-3585.
66. Basu R, et al. Th22 cells are an important source of IL-22 for host protection against enteropathogenic bacteria. Immunity 2012;37:1061-1075.
67. Stockinger B, Hirota K, Duarte J, Veldhoen M. External influences on the immune system via activation of the aryl hydrocarbon receptor. Semin Immunol 2011;23:99-105.
68. H17 differentiation by preventing Runx1-mediated activation of the gene encoding RORγt. Nat Immunol 2011;12:96-104.
69. Gessner MA, et al. Dectin-1-dependent interleukin-22 contributes to early innate lung defense against Aspergillus fumigatus. Infect Immun 2012;80:410-417.
70. lo) CD4 T cells are controlled directly by IL-10 and cause IL-22-dependent intestinal pathology. J Exp Med 2011;208:1027-1040.
71. Sonnenberg GF, Fouser LA, Artis D. Border patrol: regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22. Nat Immunol 2011;12:383-390.
72. Sonnenberg GF, Nair MG, Kirn TJ, Zaph C, Fouser LA, Artis D. Pathological versus protective functions of IL-22 in airway inflammation are regulated by IL-17A. J Exp Med 2010;207:1293-1305.
73. Andoh A, et al. Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts. Gastroenterology 2005;129:969-984.
74. Ikeuchi H, et al. Expression of interleukin-22 in rheumatoid arthritis: potential role as a proinflammatory cytokine. Arthritis Rheum 2005;52:1037-1046.
75. Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R. IL-22 increases the innate immunity of tissues. Immunity 2004;21:241-254.
76. Wolk K, et al. IL-22 induces lipopolysaccharide-binding protein in hepatocytes: a potential systemic role of IL-22 in Crohn's disease. J Immunol 2007;178:5973-5981.
77. Wolk K, et al. IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis. Eur J Immunol 2006;36:1309-1323.
78. Yang Y, et al. T-bet is essential for encephalitogenicity of both Th1 and Th17 cells. J Exp Med 2009;206:1549-1564.
79. Ferber IA, et al. Mice with a disrupted IFN-γ gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE). J Immunol 1996;156:5-7.
80. Willenborg DO, Fordham S, Bernard CC, Cowden WB, Ramshaw IA. IFN-γ plays a critical down-regulatory role in the induction and effector phase of myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis. J Immunol 1996;157:3223-3227.
81. Zhang GX, et al. Induction of experimental autoimmune encephalomyelitis in IL-12 receptor-beta 2-deficient mice: IL-12 responsiveness is not required in the pathogenesis of inflammatory demyelination in the central nervous system. J Immunol 2003;170:2153-2160.
82. Becher B, Durell BG, Noelle RJ. Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12. J Clin Invest 2002;110:493-497.
83. Bettelli E, Sullivan B, Szabo SJ, Sobel RA, Glimcher LH, Kuchroo VK. Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis. J Exp Med 2004;200:79-87.
84. Haak S, et al. IL-17A and IL-17F do not contribute vitally to autoimmune neuro-inflammation in mice. J Clin Invest 2009;119:61-69.
85. Kreymborg K, et al. IL-22 is expressed by Th17 cells in an IL-23-dependent fashion, but not required for the development of autoimmune encephalomyelitis. J Immunol 2007;179:8098-8104.
86. Gutcher I, Becher B. APC-derived cytokines and T cell polarization in autoimmune inflammation. J Clin Invest 2007;117:1119-1127.
87. Codarri L, et al. RORγt drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation. Nat Immunol 2011;12:560-567.
88. H17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF. Nat Immunol 2011;12:568-575.
89. Mcgeachy MJ, et al. The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat Immunol 2009;10:314-324.
90. Ciofani M, et al. A validated regulatory network for Th17 cell specification. Cell 2012;151:289-303.
91. Glasmacher E, et al. A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes. Science 2012;338:975-980.
92. Li P, et al. BATF-JUN is critical for IRF4-mediated transcription in T cells. Nature 2012;490:543-546.
93. Vahedi G, et al. STATs shape the active enhancer landscape of T cell populations. Cell 2012;151:981-993.
94. Durant L, et al. Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis. Immunity 2010;32:605-615.
95. Ivanov II, Zhou L, Littman DR. Transcriptional regulation of Th17 cell differentiation. Semin Immunol 2007;19:409-417.
96. H17 differentiation. Nature 2009;460:405-409.
97. Lohoff M, Mak TW. Roles of interferon-regulatory factors in T-helper-cell differentiation. Nat Rev Immunol 2005;5:125-135.
98. Hu CM, Jang SY, Fanzo JC, Pernis AB. Modulation of T cell cytokine production by interferon regulatory factor-4. J Biol Chem 2002;277:49238-49246.
99. Mukasa R, et al. Epigenetic instability of cytokine and transcription factor gene loci underlies plasticity of the T helper 17 cell lineage. Immunity 2010;32:616-627.
100. Schulz EG, Mariani L, Radbruch A, Höfer T. Sequential polarization and imprinting of type 1 T helper lymphocytes by interferon-γ and interleukin-12. Immunity 2009;30:673-683.
101. Ho IC, Lo D, Glimcher LH. c-maf promotes T helper cell type 2 (Th2) and attenuates Th1 differentiation by both interleukin 4-dependent and -independent mechanisms. J Exp Med 1998;188:1859-1866.
102. Samstein RM, et al. Foxp3 exploits a pre-existent enhancer landscape for regulatory T cell lineage specification. Cell 2012;151:153-166.
103. H17 cell differentiation by antagonizing RORγt activity. Nature 2011;472:486-490.
104. H17 differentiation and autoimmunity by a synthetic ROR ligand. Nature 2011;472:491-494.