TGF-β function in immune suppression

Current Topics in Microbiology and Immunology

Volumn 350, Issue , 2010, Pages 127-147

  Yoshimura, Akihiko ^a,b   Muto, Go ^a  

^a KEIO UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^b JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

GAMMA INTERFERON; INTERLEUKIN 12; INTERLEUKIN 17; INTERLEUKIN 2; INTERLEUKIN 4; INTERLEUKIN 6; SMAD1 PROTEIN; SMAD2 PROTEIN; SMAD3 PROTEIN; SMAD6 PROTEIN; SUPPRESSOR OF CYTOKINE SIGNALING 1; TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA; CYTOKINE; FORKHEAD TRANSCRIPTION FACTOR; FOXP3 PROTEIN, HUMAN; SMAD PROTEIN;

ALLERGIC ENCEPHALOMYELITIS; ARTHRITIS; ARTICLE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CYTOKINE PRODUCTION; EFFECTOR CELL; HELPER CELL; IMMUNE RESPONSE; IMMUNOREGULATION; LYMPHOCYTE DIFFERENTIATION; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; SIGNAL TRANSDUCTION; T LYMPHOCYTE ACTIVATION; TH17 CELL; ANIMAL; C57BL MOUSE; CELL DIFFERENTIATION; CYTOLOGY; GENETICS; HUMAN; IMMUNOLOGY; IMMUNOSUPPRESSIVE TREATMENT; METABOLISM; MOUSE; REVIEW;

ANIMALS; CELL DIFFERENTIATION; CYTOKINES; FORKHEAD TRANSCRIPTION FACTORS; HUMANS; IMMUNOSUPPRESSION; MICE; MICE, INBRED C57BL; SIGNAL TRANSDUCTION; SMAD PROTEINS; T-LYMPHOCYTES, REGULATORY; TH17 CELLS; TRANSFORMING GROWTH FACTOR BETA;

EID: 84862874597     PISSN: 0070217X     EISSN: None     Source Type: Book Series    
DOI: 10.1007/82-2010-87     Document Type: Article

References (123)

1. Afkarian M, Sedy JR, Yang J, Jacobson NG, Cereb N et al (2002) T-bet is a STAT1-induced regulator of IL-12R expression in naive CD4+ T cells. Nat Immunol 3:549-557 (Pubitemid 34662307)
2. Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ, Gurney AL (2003) Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem 278:1910-1914 (Pubitemid 36801431)
3. Aluwihare P, Mu Z, Zhao Z, Yu D, Weinreb PH, Horan GS, Violette SM, Munger JS (2009) Mice that lack activity of alphavbeta6- and alphavbeta8-integrins reproduce the abnormalities of Tgfb1- and Tgfb3-null mice. J Cell Sci 122:227-232
4. Annes JP, Munger JS, Rifkin DB (2003) Making sense of latent TGF b activation. J Cell Sci 116:217-224 (Pubitemid 36163863)
5. Bauquet AT, Jin H, Paterson AM, Mitsdoerffer M, Ho IC, Sharpe AH, Kuchroo VK (2009) The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells. Nat Immunol 10(2):167-175
6. Belladonna ML, Volpi C, Bianchi R, Vacca C, Orabona C, Pallotta MT, Boon L, Gizzi S, Fioretti MC, Grohmann U, Puccetti P (2008) Cutting edge: Autocrine TGF-beta sustains default tolerogenesis by IDO-competent dendritic cells. J Immunol 181(8):5194-5198
7. Bettelli E, Dastrange M, Oukka M (2005) Foxp3 interacts with nuclear factor of activated T cells and NF-kappa B to repress cytokine gene expression and effector functions of T helper cells. Proc Natl Acad Sci USA 102:5138-5143
8. Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, Weiner HL, Kuchroo VK (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441:235-238
9. Bommireddy R, Engle SJ, Ormsby I, Boivin GP, Babcock GF, Doetschman T (2004) Elimination of both CD4+ and CD8+ T cells but not B cells eliminates inflammation and prolongs the survival of TGFbeta1-deficient mice. Cell Immunol 232:96-104 (Pubitemid 40732724)
10. Brabletz T, Pfeuffer I, Schorr E, Siebelt F, Wirth T, Serfling E (1993) Transforming growth factor b and cyclosporin A inhibit the inducible activity of the interleukin-2 gene in T cells through a noncanonical octamer-binding site. Mol Cell Biol 13:1155-1162 (Pubitemid 23040282)
11. Burchill MA, Yang J, Vogtenhuber C, Blazar BR, Farrar MA (2007) IL-2 receptor beta-dependent STAT5 activation is required for the develop- ment of Foxp3+ regulatory T cells. J Immunol 178:280-290 (Pubitemid 46033611)
12. Caretto D, Katzman SD, Villarino AV, Gallo E, Abbas AK (2010) Cutting edge: The Th1 response inhibits the generation of peripheral regulatory T cells. J Immunol 184(1):30-34
13. Chang H, Brown CW, Matzuk MM (2002) Genetic analysis of the mammalian transforming growth factor-beta superfamily. Endocr Rev 23:787-823 (Pubitemid 35454589)
14. Chang JH, KimYJ, Han SH, KangCY(2009) IFN-gamma-STAT1 signal regulates the differentiation of inducible Treg: Potential role for ROS-mediated apoptosis. Eur J Immunol 39(5):1241-1251
15. Chaudhry A, Rudra D, Treuting P, Samstein RM, Liang Y, Kas A, Rudensky AY (2009) CD4+ regulatory T cells control TH17 responses in a Stat3-dependent manner. Science 326 (5955):986-991
16. Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, McGrady G, Wahl SM (2003) Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 198(12):1875-1886 (Pubitemid 38032120)
17. Chen Z, Laurence A, Kanno Y, Pacher-Zavisin M, Zhu BM, Tato C, Yoshimura A, Hennighausen L, O'Shea JJ (2006) Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells. Proc Natl Acad Sci USA 103:8137-8142 (Pubitemid 43801065)
18. Chen ML, Yan BS, Bando Y, Kuchroo VK, Weiner HL (2008) Latency-associated peptide identifies a novel CD4+CD25+ regulatory T cell subset with TGFb-mediated function and enhanced suppression of experimental autoimmune encephalomyelitis. J Immunol 180:7327-7337
19. Cho ML, Kang JW, Moon YM, Nam HJ, Jhun JY, Heo SB, Jin HT, Min SY, Ju JH, Park KS, Cho YG, Yoon CH, Park SH, Sung YC, Kim HY (2006) STAT3 and NF-kappaB signal pathway is required for IL-23-mediated IL-17 production in spontaneous arthritis animal model IL-1 receptor antagonist-deficient mice. J Immunol 176:5652-5661
20. Cottrez F, Groux H (2001) Regulation of TGF-beta response during T cell activation is modulated by IL-10. J Immunol 167:773-778 (Pubitemid 32660831)
21. Das J, Ren G, Zhang L, Roberts AI, Zhao X, Bothwell AL, Van Kaer L, Shi Y, Das G (2009) Transforming growth factor beta is dispensable for the molecular orchestration of Th17 cell differentiation. J Exp Med 206(13):2407-2416
22. Davidson TS, DiPaolo RJ, Andersson J, Shevach EM (2007) Cutting Edge: IL-2 is essential for TGF-beta-mediated induction of Foxp3+ T regulatory cells. J Immunol 178:4022-4026 (Pubitemid 46492349)
23. de Beaucoudrey L, Puel A, Filipe-Santos O, Cobat A, Ghandil P et al (2008) Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells. J Exp Med 205:1543
24. Derynck R, Zhang YE (2003) Smad-dependent and Smad-independent pathways in TGF-b family signalling. Nature 425:577-584 (Pubitemid 37280136)
25. Diebold RJ, Eis MJ, Yin M, Ormsby I, Boivin GP, Darrow BJ, Saffitz JE, Doetschman T (1995) Early-onset multifocal inflammation in the transforming growth factor beta 1-null mouse is lymphocyte mediated. Proc Natl Acad Sci USA 92:12215-12219
26. Ding A, Nathan CF, Graycar J, Derynck R, Stuehr DJ, Srimal S (1990) Macrophage deactivating factor and transforming growth factors-beta 1 -beta 2 and -beta 3 inhibit induction of macrophage nitrogen oxide synthesis by IFN-gamma. J Immunol 145:940-944 (Pubitemid 20231287)
27. Dong C (2008) TH17 cells in development: An updated view of their molecular identity and genetic programming. Nat Rev Immunol 8(5):337-348 (Pubitemid 351595217)
28. Eickelberg O, Pansky A, Koehler E, Bihl M, Tamm M, Hildebrand P, Perruchoud AP, Kashgarian M, Roth M (2001) Molecular mechanisms of TGF-(beta) antagonism by interferon (gamma) and cyclosporine A in lung fibroblasts. Faseb J 15:797-806 (Pubitemid 32245998)
29. Fadok VA, Bratton DL, Konowal A, Freed PW, Westcott JY, Henson PM (1998) Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-b, PGE2, and PAF. J Clin Invest 101:890-898 (Pubitemid 28096086)
30. Fontenot JD, Gavin MA, Rudensky AY (2003) Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 4:330-336 (Pubitemid 36432314)
31. Geissmann F, Revy P, Regnault A, Lepelletier Y, Dy M, Brousse N, Amigorena S, Hermine O, Durandy A (1999) TGF-b1 prevents the noncognate maturation of human dendritic Langerhans cells. J Immunol 162:4567-4575 (Pubitemid 29314856)
32. Ghosh AK, Yuan W, Mori Y, Chen S, Varga J (2001) Antagonistic regulation of type I collagen gene expression by interferon-gamma and transforming growth factor-beta. Integration at the level of p300/CBP transcriptional coactivators. J Biol Chem 276:11041-11048 (Pubitemid 38089285)
33. Glimcher LH, Murphy KM (2000) Lineage commitment in the immune system: The T helper lymphocyte grows up. Genes Dev 14:1693-1711 (Pubitemid 30602989)
34. Gorelik L, Flavell RA (2000) Abrogation of TGFb signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease. Immunity 12:171-181 (Pubitemid 30398631)
35. Gorelik L, Constant S, Flavell RA (2002a) Mechanism of transforming growth factor b-induced inhibition of T helper type 1 differentiation. J Exp Med 195:1499-1505 (Pubitemid 34602827)
36. Gorelik L, Fields PE, Flavell RA (2002b) Cutting edge: TGF-b inhibits Th type 2 development through inhibition of GATA-3 expression. J Immunol 165:4773-4777
37. Govinden R, Bhoola KD (2003) Genealogy, expression, and cellular function of transforming growth factor-beta. Pharmacol Ther 98:257-265 (Pubitemid 36513779)
38. Hannon GJ, Beach D (1994) p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest. Nature 371:257-261
39. Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT (2005) Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6:1123-1132 (Pubitemid 41541790)
40. He W, Dorn DC, Erdjument-Bromage H, Tempst P, Moore MA, Massague J (2006) Hematopoiesis controlled by distinct TIF1gamma and Smad4 branches of the TGFbeta pathway. Cell 125:929-941 (Pubitemid 43795187)
41. Heath VL, Murphy EE, Crain C, Tomlinson MG, O'Garra A (2000) TGF-b1 down-regulates Th2 development and results in decreased IL-4-induced STAT6 activation and GATA-3 expression. Eur J Immunol 30:2639-2649
42. Horino J, Fujimoto M, Terabe F, Serada S, Takahashi T, SomaY, TanakaK, Chinen T,Yoshimura A, Nomura S, Kawase I, Hayashi N,Kishimoto T, Naka T (2008) Suppressor of cytokine signaling-1 ameliorates dextran sulfate sodium-induced colitis in mice. Int Immunol 20(6):753-762 (Pubitemid 351791519)
43. Huber M, Brüstle A, Reinhard K, Guralnik A, Walter G, Mahiny A, von Löw E, Lohoff M (2008) IRF4 is essential for IL-21-mediated induction, amplification, and stabilization of the Th17 phenotype. Proc Natl Acad Sci USA 105(52):20846-20851
44. Huse M, Muir TW, Xu L, Chen YG, Kuriyan J, Massague J (2001) The TGF b receptor activation process: An inhibitor- to substrate-binding switch. Mol Cell 8:671-682 (Pubitemid 32946943)
45. Ichiyama K, Yoshida H, Wakabayashi Y, Chinen T, Saeki K, Nakaya M, Takaesu G, Hori S, Yoshimura A, Kobayashi T (2008) Foxp3 inhibits RORgammat-mediated IL-17A mRNA transcription through direct interaction with RORgammat. J Biol Chem 283(25):17003-17008
46. Infante-Duarte C, Horton HF, Byrne MC, Kamradt T (2000) Microbial lipopeptides induce the production of IL-17 in Th cells. J Immunol 165:6107-6115
47. Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, Cua DJ, Littman DR (2006) The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126:1121-1133 (Pubitemid 44380299)
48. Jaksits S, Kriehuber E, Charbonnier AS, Rappersberger K, Stingl G, Maurer D (1999) CD34+ cellderived CD14+ precursor cells develop into Langerhans cells in a TGF-b1-dependent manner. J Immunol 163:4869-4877 (Pubitemid 29501251)
49. Kim BG, Li C, Qiao W, Mamura M, Kasprzak B, Anver M, Wolfraim L, Hong S, Mushinski E, Potter M, Kim SJ, Fu XY, Deng C, Letterio JJ (2006) Smad4 signalling in T cells is required for suppression of gastrointestinal cancer. Nature 441:1015-1019 (Pubitemid 43980359)
50. Kinjyo I, Inoue H, Hamano S, Fukuyama S, Yoshimura T, Koga K, Takaki H, Himeno K, Takaesu G, Kobayashi T, Yoshimura A (2006) Loss of SOCS3 in T helper cells resulted in reduced immune responses and hyperproduction of interleukin 10 and transforming growth factor-beta 1. J Exp Med 203(4):1021-1031
51. Korn T, Oukka M, Kuchroo V, Bettelli E (2007a) Th17 cells: Effector T cells with inflammatory properties. Semin Immunol 19(6):362-371 (Pubitemid 351274046)
52. Korn T, Bettelli E, Gao W, Awasthi A, Jager A, Strom TB, Oukka M, Kuchroo VK (2007b) IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature 448:484-487 (Pubitemid 47123515)
53. Kubo M, Hanada T, Yoshimura A (2003) Suppressors of cytokine signaling and immunity. Nat Immunol 4:1169-1176 (Pubitemid 37540685)
54. Kulkarni AB, Huh CG, Becker D, Geiser A, Lyght M, Flanders KC, Roberts AB, Sporn MB, Ward JM, Karlsson S (1993) Transforming growth factor b1 null mutation in mice causes excessive inflammatory response and early death. Proc Natl Acad Sci USA 90:770-774 (Pubitemid 23028947)
55. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, McClanahan T, Kastelein RA, Cua DJ (2005) IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 201:233-240 (Pubitemid 40189432)
56. Laouar Y, Sutterwala FS, Gorelik L, Flavell RA (2005) Transforming growth factor-beta controls T helper type 1 cell development through regulation of natural killer cell interferon-gamma. Nat Immunol 6:600-607 (Pubitemid 41710731)
57. Letterio JJ, Geiser AG, Kulkarni AB, Dang H, Kong L, Nakabayashi T, Mackall CL, Gress RE, Roberts AB (1996) Autoimmunity associated with TGF-beta1-deficiency in mice is dependent on MHC class II antigen expressions II antigen expression. J Clin Invest 98:2109-2119 (Pubitemid 26376300)
58. Li MO, Flavell RA (2008a) Contextual regulation of inflammation: A duet by transforming growth factor-beta and interleukin-10. Immunity 28(4):468-476 (Pubitemid 351467045)
59. Li MO, Flavell RA (2008b) TGF-beta: A master of all T cell trades. Cell 134(3):392-404
60. Li MO, Wan YY, Sanjabi S, Robertson AK, Flavell RA (2006a) Transforming growth factor-beta regulation of immune responses. Annu Rev Immunol 24:99-146
61. Li MO, Sanjabi S, Flavell RA (2006b) Transforming growth factor-b controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and -independent mechanisms. Immunity 25:455-471 (Pubitemid 44354214)
62. Li MO, Wan YY, Flavell RA (2007) T cell-produced transforming growth factor-beta1 controls T cell tolerance and regulates Th1- and Th17-cell differentiation. Immunity 26(5):579-591 (Pubitemid 46756347)
63. Ludviksson BR, Seegers D, Resnick AS, Strober W (2000) The effect of TGF-beta1 on immune responses of naive versus memory CD4+ Th1/Th2 T cells. Eur J Immunol 30:2101-2111 (Pubitemid 30456207)
64. Ma CS, Chew GYJ, Simpson N et al (2008) Deficiency of Th17 cells in hyper IgE syndrome due to mutations in STAT3. J Exp Med 205:1551
65. Mangan PR, Harrington LE, O'Quinn DB, Helms WS, Bullard DC, Elson CO, Hatton RD, Wahl SM, Schoeb TR, Weaver CT (2006) Transforming growth factor-beta induces development of the T(H)17 lineage. Nature 441:231-234
66. Marie JC, Letterio JJ, Gavin M, Rudensky AY (2005) TGF-beta1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells. J Exp Med 201(7):1061-1067 (Pubitemid 40524674)
67. Marie JC, Liggitt D, Rudensky AY (2006) Cellular mechanisms of fatal early-onset autoimmunity in mice with the T cell-specific targeting of transforming growth factor-beta receptor. Immunity 25:441-454 (Pubitemid 44354215)
68. Massague J (1998) TGF-beta signal transduction. Annu Rev Biochem 67:753-791
69. Matsumura Y, Kobayashi T, Ichiyama K, Yoshida R, Hashimoto M, Takimoto T, Tanaka K, Chinen T, Shichita T, Wyss-Coray T, Sato K, Yoshimura A (2007) Selective expansion of foxp3-positive regulatory T cells and immunosuppression by suppressors of cytokine signaling 3-deficient dendritic cells. J Immunol 179(4):2170-2179
70. McKarns SC, Schwartz RH, Kaminski NE (2004) Smad3 is essential for TGF-beta 1 to suppress IL-2 production and TCR-induced proliferation, but not IL-2-induced proliferation. J Immunol 172:4275-4284 (Pubitemid 38375241)
71. Mempel TR, Pittet MJ, Khazaie K, Weninger W, Weissleder R, von Boehmer H, von Andrian UH (2006) Regulatory T cells reversibly suppress cytotoxic T cell function independent of effector differentiation. Immunity 25:129-141 (Pubitemid 44066829)
72. Milner JD, Brenchley JM, Laurence A et al (2008) Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature 452:773
73. Mitani T, Terashima M, Yoshimura H, Nariai Y, Tanigawa Y (2005) TGF-beta1 enhances degradation of IFN-gamma-induced iNOS protein via proteasomes in RAW 264.7 cells. Nitric Oxide 13:78-87 (Pubitemid 40853972)
74. Miyazono K, Maeda S, Imamura T (2004) Coordinate regulation of cell growth and differentiation by TGF-b superfamily and Runx proteins. Oncogene 23:4232-4237 (Pubitemid 38758589)
75. Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A (2001) Interleukin-10 and the interleukin- 10 receptor. Annu Rev Immunol 19:683-765
76. 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 (Pubitemid 47076203)
77. Naiki Y, Michelsen KS, Zhang W, Chen S, Doherty TM, Arditi M (2005) Transforming growth factor-b differentially inhibits MyD88-dependent, but not TRAM- and TRIF-dependent, lipopolysaccharide- induced TLR4 signaling. J Biol Chem 280:5491-5495 (Pubitemid 40280025)
78. Nakamura K, Kitani A, Fuss I, Pedersen A, Harada N, Nawata H, Strober W (2004) TGF-beta 1 plays an important role in the mechanism of CD4+CD25+ regulatory T cell activity in both humans and mice. J Immunol 172(2):834-842 (Pubitemid 38113739)
79. Nelson BJ, Ralph P, Green SJ, Nacy CA (1991) Differential susceptibility of activated macrophage cytotoxic effector reactions to the suppressive effects of transforming growth factor-beta 1. J Immunol 146:1849-1857
80. Nomura M, Li E (1998) Smad2 role in mesoderm formation, left-right patterning and craniofacial development. Nature 25:737-739
81. Nurieva R, Yang XO, Martinez G, Zhang Y, Panopoulos AD, Ma L, Schluns K, Tian Q, Watowich SS, Jetten AM, Dong C (2007) Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 448:480-483 (Pubitemid 47123514)
82. Ouaked N, Mantel PY, Bassin C, Burgler S, Siegmund K, Akdis CA, Schmidt-Weber CB (2009) Regulation of the foxp3 gene by the Th1 cytokines: The role of IL-27-induced STAT1. J Immunol 182(2):1041-1049
83. Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, Wang Y, Hood L, Zhu Z, Tian Q, Dong C (2005a) A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 6:1133-1141 (Pubitemid 41541791)
84. Park IK, Shultz LD, Letterio JJ, Gorham JD (2005b) TGF-beta1 inhibits T-bet induction by IFNgamma in murine CD4+ T cells through the protein tyrosine phosphatase Src homology region 2 domain-containing phosphatase-1. J Immunol 175(9):5666-5674 (Pubitemid 41508048)
85. Pesu M, Watford WT, Wei L, Xu L, Fuss I, Strober W, Andersson J, Shevach EM, Quezado M, Bouladoux N, Roebroek A, Belkaid Y, Creemers J, O'Shea JJ (2008) T-cell-expressed proprotein convertase furin is essential for maintenance of peripheral immune tolerance. Nature 455:246-250
86. Polyak K, Kato JY, Solomon MJ, Sherr CJ, Massague J, Roberts JM, Koff A (1994) p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest. Genes Dev 8:9-22
87. Reardon C, McKay DM (2007) TGF-beta suppresses IFN-gamma-STAT1-dependent gene transcription by enhancing STAT1-PIAS1 interactions in epithelia but not monocytes/ macrophages. J Immunol 178(7):4284-4295 (Pubitemid 46492379)
88. Rubtsov YP, Rudensky AY (2007) TGFbeta signalling in control of T-cell-mediated self-reactivity. Nat Rev Immunol 7(6):443-453 (Pubitemid 46834850)
89. Rudner LA, Lin JT, Park IK, Cates JM, Dyer DA, Franz DM, Fresnch MA, Duncan EM, White HD, Gorham JD (2003) Necroinflammatory liver disease in BALB/c background, TGF-beta 1-deficient mice requires CD4+ T cells. J Immunol 170:4785-4792 (Pubitemid 36519988)
90. Ruegemer JJ, Ho SN, Augustine JA, Schlager JW, Bell MP, McKean DJ, Abraham RT (1990) Regulatory effects of transforming growth factor-beta on IL-2- and IL-4-dependent T cellcycle progression. J Immunol 144(5):1767-1776 (Pubitemid 20094008)
91. Sakaguchi S (2004) Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 22:531-562 (Pubitemid 38680433)
92. Samon JB, Champhekar A, Minter LM, Telfer JC, Miele L, Fauq A, Das P, Golde TE, Osborne BA (2008) Notch1 and TGFbeta1 cooperatively regulate Foxp3 expression and the maintenance of peripheral regulatory T cells. Blood 112(5):1813-1821
93. Shull MM, Ormsby I, Kier AB, Pawlowski S, Diebold RJ, Yin M, Allen R, Sidman C, Proetzel G, Calvin D et al (1992) Targeted disruption of the mouse transforming growth factor-b1 gene results in multifocal inflammatory disease. Nature 359:693-699
94. Strobl H, Knapp W (1999) TGF-b1 regulation of dendritic cells. Microbes Infect 1:1283-1289
95. Strobl H, Riedl E, Scheinecker C, Bello-Fernandez C, Pickl WF, Rappersberger K, Majdic O, Knapp W (1996) TGF-b1 promotes in vitro development of dendritic cells from CD34+ hemopoietic progenitors. J Immunol 157:1499-1507 (Pubitemid 126449086)
96. Takaki H, Minoda Y, Koga K, Takaesu G, Yoshimura A, Kobayashi T (2006) TGF-beta1 suppresses IFN-gamma-induced NO production in macrophages by suppressing STAT1 activation and accelerating iNOS protein degradation. Genes Cells 11(8):871-882 (Pubitemid 44101355)
97. Takaki H, Ichiyama K, Koga K, Chinen T, Takaesu G, Sugiyama Y, Kato S, Yoshimura A, Kobayashi T (2008) STAT6 Inhibits TGF-b-1-mediated Foxp3 induction through direct binding to the Foxp3 promoter, which is reverted by retinoic acid receptor. J Biol Chem 283 (22):14955-14962
98. Takimoto T, Wakabayashi Y, Sekiya T, Inoue N, Morita R, Ichiyama K, Takahashi R, Asakawa M, Muto G, Mori T, Hasegawa E, Shizuya S, Hara T, Nomura M, Yoshimura A (2010) Smad2 and Smad3 are redundantly essential for the TGF-b-mediated regulation of regulatory T plasticity and Th1 development. J Immunol 185 (2):842-855
99. Tanaka K, Ichiyama K, Hashimoto M, Yoshida H, Takimoto T, Takaesu G, Torisu T, Hanada T, Yasukawa H, Fukuyama S, Inoue H, Nakanishi Y, Kobayashi T, Yoshimura A (2008) Loss of suppressor of cytokine signaling 1 in helper T cells leads to defective Th17 differentiation by enhancing antagonistic effects of IFN-gamma on STAT3 and Smads. J Immunol 180 (6):3746-3756
100. Taylor AW (2009) Review of the activation of TGF-b in immunity. J Leukocyte Biol 85:29-33
101. Tone Y, Furuuchi K, Kojima Y, Tykocinski ML, Greene MI, Tone M (2008) Smad3 and NFAT cooperate to induce Foxp3 expression through its enhancer. Nat Immunol 9(2):194-202
102. Travis MA, Reizis B, Melton AC, Masteller E, Tang Q, Proctor JM, Wang Y, Bernstein X, Huang X, Reichardt LF, Bluestone JA, Sheppard D (2007) avb8 on dendritic cells causes autoimmunity and colitis in mice. Nature 449:361-365
103. Tzachanis D, Freeman GJ, Hirano N, van Puijenbroek AA, Delfs MW, Berezovskaya A, Nadler LM, Boussiotis VA (2001) Tob is a negative regulator of activation that is expressed in anergic and quiescent T cells. Nat Immunol 2:1174-1182 (Pubitemid 33130153)
104. Ulloa L, Doody J, Massague J (1999) Inhibition of transforming growth factor-beta/SMAD signalling by the interferon-gamma/STAT pathway. Nature 397:710-713
105. Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B (2006a) TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24:179-189 (Pubitemid 43214587)
106. Veldhoen M, Hocking RJ, Flavell RA, Stockinger B (2006b) Signals mediated by transforming growth factor-beta initiate autoimmune encephalomyelitis, but chronic inflammation is needed to sustain disease. Nat Immunol 7(11):1151-1156 (Pubitemid 44594310)
107. Veldhoen M, Uyttenhove C, van Snick J, Helmby H, Westendorf A, Buer J, Martin B, Wilhelm C, Stockinger B (2008) Transforming growth factor-beta 'reprograms' the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset. Nat Immunol 9(12):1341-1346
108. Wan YY, Flavell RA (2007) 'Yin-Yang' functions of transforming growth factor-beta and T regulatory cells in immune regulation. Immunol Rev 220:199-213 (Pubitemid 350064011)
109. Werner F, Jain MK, Feinberg MW, Sibinga NE, Pellacani A, Wiesel P, Chin MT, Topper JN, Perrella MA, Lee ME (2000) Transforming growth factor-b1 inhibition of macrophage activation is mediated via Smad3. J Biol Chem 275:36653-36658 (Pubitemid 32002067)
110. Wolfraim LA, Walz TM, James Z, Fernandez T, Letterio JJ (2004) p21Cip1 and p27Kip1 act in synergy to alter the sensitivity of naive T cells to TGF-beta-mediated G1 arrest through modulation of IL-2 responsiveness. J Immunol 173:3093-3102 (Pubitemid 39142015)
111. Yamazaki S, Patel M, Harper A, Bonito A, Fukuyama H, Pack M, Tarbell KV, Talmor M, Ravetch JV, Inaba K, Steinman RM (2006) Effective expansion of alloantigen-specific Foxp3+ CD25+ CD4+ regulatory T cells by dendritic cells during the mixed leukocyte reaction. Proc Natl Acad Sci USA 103(8):2758-2763
112. Yamazaki S, Dudziak D, Heidkamp GF, Fiorese C, Bonito AJ, Inaba K, Nussenzweig MC, Steinman RM (2008) CD8+ CD205+ splenic dendritic cells are specialized to induce Foxp3+ regulatory T cells. J Immunol 181(10):6923-6933
113. Yang XO, Letterio JJ, Lechleider RJ, Chen L, Hayman R, Gu H, Roberts AB, Deng C (1999) Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF-b. EMBO J 18:1280-1291 (Pubitemid 29110312)
114. Yang Y, Ochando J, Yopp A, Bromberg JS, Ding Y (2005) IL-6 plays a unique role in initiating c-Maf expression during early stage of CD4 T cell activation. J Immunol 174(5):2720-2729 (Pubitemid 40279687)
115. Yang XO, Panopoulos AD, Nurieva R, Chang SH, Wang D, Watowich SS, Dong C (2007) STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J Biol Chem 282:9358-9363 (Pubitemid 47104613)
116. Yang XO, Nurieva R, Martinez GJ, Kang HS, Chung Y, Pappu BP, Shah B, Chang SH, Schluns KS, Watowich SS, Feng XH, Jetten AM, Dong C (2008) Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity 29(1):44-56
117. Yao Z, Kanno Y, Kerenyi M, Stephens G, Durant L, Watford WT, Laurence A, Robinson GW, Shevach EM, Moriggl R, Hennighausen L, Wu C, O'Shea JJ (2007) Nonredundant roles for Stat5a/b in directly regulating Foxp3. Blood 109:4368-4375 (Pubitemid 46743405)
118. Yongzhong L, Zhang P, Li J, Kulkarni AB, Perruche S, Chen W (2008) A critical function for TGF-b signaling in the development of natural CD4+CD25+Foxp3+regulatory T cells. Nat Immunol 9:632-640 (Pubitemid 351712634)
119. Yoshimura A, Naka T, Kubo M (2007) SOCS proteins, cytokine signalling and immune regulation. Nat Rev Immunol 7:454-465 (Pubitemid 46834848)
120. Yu L, Hebert MC, Zhang YE (2002) TGF-b receptor-activated p38 MAP kinase mediates Smad-independent TGF-b responses. EMBO J 21:3749-3759 (Pubitemid 34787048)
121. Zhang Y, Zhang YY, Ogata M, Chen P, Harada A, Hashimoto S, Matsushima K (1999) Transforming growth factor-b1 polarizes murine hematopoietic progenitor cells to generate Langerhans cell-like dendritic cells through a monocyte/macrophage differentiation pathway. Blood 93:1208-1220 (Pubitemid 29076135)
122. Zheng Y, Josefowicz S, Chaudhry A, Peng XP, Forbush K, Rudensky AY (2010) Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature 463(7282):808-812
123. Zhou L, Lopes JE, Chong MM, Ivanov II, Min R, Victora GD, Shen Y, Du J, Rubtsov YP, Rudensky AY, Ziegler SF, Littman DR (2008) TGF-beta-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORgt function. Nature 453:236-240 (Pubitemid 351667978)