Smad2 and Smad3 are redundantly essential for the TGF-β-mediated regulation of regulatory T plasticity and Th1 development

Journal of Immunology

Volumn 185, Issue 2, 2010, Pages 842-855

  Takimoto, Tomohito ^a,c   Wakabayashi, Yu ^a   Sekiya, Takashi ^a   Inoue, Naoko ^a   Morita, Rimpei ^a   Ichiyama, Kenji ^a   Takahashi, Reiko ^a   Asakawa, Mayako ^a   Muto, Go ^a   Mori, Tomoaki ^a   Hasegawa, Eiichi ^a   Shizuya, Saika ^d   Hara, Toshiro ^c   Nomura, Masatoshi ^c   Yoshimura, Akihiko ^a,b  

^a KEIO UNIVERSITY   (Japan)

^b JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

^c KYUSHU UNIVERSITY   (Japan)

^d WAKAYAMA MEDICAL UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

GAMMA INTERFERON; SMAD2 PROTEIN; SMAD3 PROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR FOXP3; TRANSCRIPTION FACTOR ROR GAMMA T; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG; ALPHA E INTEGRINS; ALPHA INTEGRIN; FORKHEAD TRANSCRIPTION FACTOR; FOXP3 PROTEIN, MOUSE; LEUKOCYTE ANTIGEN; RETINOID RELATED ORPHAN RECEPTOR GAMMA; SMAD2 PROTEIN, MOUSE; SMAD3 PROTEIN, MOUSE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CD4+ T LYMPHOCYTE; CELL DIFFERENTIATION; CELL MATURATION; CONTROLLED STUDY; GENETIC TRANSCRIPTION; INFLAMMATION; INTERFERON PRODUCTION; MOUSE; NONHUMAN; PHENOTYPE; PHENOTYPIC PLASTICITY; PRIORITY JOURNAL; REGULATORY MECHANISM; REGULATORY T LYMPHOCYTE; TH1 CELL; WESTERN BLOTTING; ANIMAL; C57BL MOUSE; CYTOLOGY; DNA MICROARRAY; FLOW CYTOMETRY; GENE EXPRESSION PROFILING; GENETICS; METABOLISM; MOUSE MUTANT; PHYSIOLOGY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION;

ANIMALS; ANTIGENS, CD; BLOTTING, WESTERN; CD4-POSITIVE T-LYMPHOCYTES; CELL DIFFERENTIATION; FLOW CYTOMETRY; FORKHEAD TRANSCRIPTION FACTORS; GENE EXPRESSION PROFILING; INFLAMMATION; INTEGRIN ALPHA CHAINS; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; NUCLEAR RECEPTOR SUBFAMILY 1, GROUP F, MEMBER 3; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; SMAD2 PROTEIN; SMAD3 PROTEIN; T-LYMPHOCYTES, REGULATORY; TH1 CELLS; TRANSFORMING GROWTH FACTOR BETA;

EID: 77955498891     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.0904100     Document Type: Article

References (57)

1. Letterio, J. J., and A. B. Roberts. 1998. Regulation of immune responses by TGF-beta. Annu. Rev. Immunol. 16: 137-161.
2. Gorelik, L., and R. A. Flavell. 2002. Transforming growth factor-beta in T-cell biology. Nat. Rev. Immunol. 2: 46-53.
3. Shull, M. M., I. Ormsby, A. B. Kier, S. Pawlowski, R. J. Diebold, M. Yin, R. Allen, C. Sidman, G. Proetzel, D. Calvin, et al. 1992. Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature 359: 693-699.
4. Kulkarni, A. B., C. G. Huh, D. Becker, A. Geiser, M. Lyght, K. C. Flanders, A. B. Roberts, M. B. Sporn, J. M. Ward, and S. Karlsson. 1993. Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death. Proc. Natl. Acad. Sci. USA 90: 770-774.
5. Gorelik, L., and R. A. Flavell. 2000. Abrogation of TGFbeta signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease. Immunity 12: 171-181.
6. Marie, J. C., D. Liggitt, and A. Y. Rudensky. 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.
7. Li, M. O., S. Sanjabi, and R. A. Flavell. 2006. Transforming growth factor-beta controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and -independent mechanisms. Immunity 25: 455-471.
8. Li, M. O., and R. A. Flavell. 2008. TGF-β: a master of all T cell trades. Cell 134: 392-404.
9. Chen, W., W. Jin, N. Hardegen, K. J. Lei, L. Li, N. Marinos, G. McGrady, and S. M. Wahl. 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: 1875-1886.
10. Hori, S., T. Nomura, and S. Sakaguchi. 2003. Control of regulatory T cell development by the transcription factor Foxp3. Science 299: 1057-1061. (Pubitemid 36222930)
11. Fontenot, J. D., M. A. Gavin, and A. Y. Rudensky. 2003. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol. 4: 330-336.
12. Bettelli, E., M. Dastrange, and M. Oukka. 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.
13. Zhou, L., J. E. Lopes, M. M. Chong, I. I. Ivanov, R. Min, G. D. Victora, Y. Shen, J. Du, Y. P. Rubtsov, A. Y. Rudensky, et al. 2008. TGF-β-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function. Nature 453: 236-240. (Pubitemid 351667978)
14. Ichiyama, K., H. Yoshida, Y. Wakabayashi, T. Chinen, K. Saeki, M. Nakaya, G. Takaesu, S. Hori, A. Yoshimura, and T. Kobayashi. 2008. Foxp3 inhibits RORgammat-mediated IL-17A mRNA transcription through direct interaction with RORgammat. J. Biol. Chem. 283: 17003-17008.
15. 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.
16. You, S., B. Leforban, C. Garcia, J. F. Bach, J. A. Bluestone, and L. Chatenoud. 2007. Adaptive TGF-βb-dependent regulatory T cells control autoimmune diabetes and are a privileged target of anti-CD3 antibody treatment. Proc. Natl. Acad. Sci. USA 104: 6335-6340.
17. Liu, Y., P. Zhang, J. Li, A. B. Kulkarni, S. Perruche, and W. Chen. 2008. A critical function for TGF-β signaling in the development of natural CD4+CD25+ Foxp3+ regulatory T cells. Nat. Immunol. 9: 632-640.
18. Massagué, J. 1998. TGF-beta signal transduction. Annu. Rev. Biochem. 67: 753-791.
19. He, W., D. C. Dorn, H. Erdjument-Bromage, P. Tempst, M. A. S. Moore, and J. Massagué. 2006. Hematopoiesis controlled by distinct TIF1gamma and Smad4 branches of the TGFbeta pathway. Cell 125: 929-941. (Pubitemid 43795187)
20. Nomura, M., and E. Li. 1998. Smad2 role in mesoderm formation, left-right patterning and craniofacial development. Nature 396: 786-790. (Pubitemid 28299489)
21. Yang, X. O., J. J. Letterio, R. J. Lechleider, L. Chen, R. Hayman, H. Gu, A. B. Roberts, and C. Deng. 1999. Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF-β. EMBO J. 18: 1280-1291.
22. Tone, Y., K. Furuuchi, Y. Kojima, M. L. Tykocinski, M. I. Greene, and M. Tone. 2008. Smad3 and NFAT cooperate to induce Foxp3 expression through its enhancer. Nat. Immunol. 9: 194-202.
23. Kim, B. G., C. Li, W. Qiao, M. Mamura, B. Kasprzak, B. Kasperczak, M. Anver, L. Wolfraim, S. Hong, E. Mushinski, et al. 2006. Smad4 signalling in T cells is required for suppression of gastrointestinal cancer. Nature 441: 1015-1019.
24. Kinjyo, I., H. Inoue, S. Hamano, S. Fukuyama, T. Yoshimura, K. Koga, H. Takaki, K. Himeno, G. Takaesu, T. Kobayashi, and A. Yoshimura. 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: 1021-1031.
25. Flanders, K. C., C. D. Sullivan, M. Fujii, A. Sowers, M. A. Anzano, A. Arabshahi, C. Major, C. Deng, A. Russo, J. B. Mitchell, and A. B. Roberts. 2002. Mice lacking Smad3 are protected against cutaneous injury induced by ionizing radiation. Am. J. Pathol. 160: 1057-1068.
26. Takaki, H., K. Ichiyama, K. Koga, T. Chinen, G. Takaesu, Y. Sugiyama, S. Kato, A. Yoshimura, and T. Kobayashi. 2008. STAT6 Inhibits TGF-beta1-mediated Foxp3 induction through direct binding to the Foxp3 promoter, which is reverted by retinoic acid receptor. J. Biol. Chem. 283: 14955-14962.
27. Tanaka, K., K. Ichiyama, M. Hashimoto, H. Yoshida, T. Takimoto, G. Takaesu, T. Torisu, T. Hanada, H. Yasukawa, S. Fukuyama, et al. 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: 3746-3756.
28. Koga, K., G. Takaesu, R. Yoshida, M. Nakaya, T. Kobayashi, I. Kinjyo, and A. Yoshimura. 2009. Cyclic adenosine monophosphate suppresses the transcription of proinflammatory cytokines via the c-Fos protein. Immunity 30: 372-383.
29. Ivanov, I. I., B. S. McKenzie, L. Zhou, C. E. Tadokoro, A. Lepelley, J. J. Lafaille, D. J. Cua, and D. R. Littman. 2006. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126: 1121-1133.
30. Langrish, C. L., Y. Chen, W. M. Blumenschein, J. Mattson, B. Basham, J. D. Sedgwick, T. McClanahan, R. A. Kastelein, and D. J. Cua. 2005. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J. Exp. Med. 201: 233-240.
31. Matsumura, Y., T. Kobayashi, K. Ichiyama, R. Yoshida, M. Hashimoto, T. Takimoto, K. Tanaka, T. Chinen, T. Shichita, T. Wyss-Coray, et al. 2007. Selective expansion of foxp3-positive regulatory T cells and immunosuppression by suppressors of cytokine signaling 3-deficient dendritic cells. J. Immunol. 179: 2170-2179.
32. Ito, R., M. Shin-Ya, T. Kishida, A. Urano, R. Takada, J. Sakagami, J. Imanishi, M. Kita, Y. Ueda, Y. Iwakura, et al. 2006. Interferon-gamma is causatively involved in experimental inflammatory bowel disease in mice. Clin. Exp. Immunol. 146: 330-338.
33. -/-) mice. World J. Gastroenterol. 12: 2455-2458.
34. Descargues, P., A. K. Sil, Y. Sano, O. Korchynskyi, G. Han, P. Owens, X. J. Wang, and M. Karin. 2008. IKKalpha is a critical coregulator of a Smad4-independent TGFbeta-Smad2/3 signaling pathway that controls keratinocyte differentiation. Proc. Natl. Acad. Sci. USA 105: 2487-2492.
35. Hill, J. A., M. Feuerer, K. Tash, S. Haxhinasto, J. Perez, R. Melamed, D. Mathis, and C. Benoist. 2007. Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature. Immunity 27: 786-800.
36. Wei, G., L. Wei, J. Zhu, C. Zang, J. Hu-Li, Z. Yao, K. Cui, Y. Kanno, T. Y. Roh, W. T. Watford, et al. 2009. Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells. Immunity 30: 155-167.
37. + Th1/Th2 T cells. Eur. J. Immunol. 30: 2101-2111.
38. + T cells in Scurfy mice that display both CD103-dependent and independent inflammation. J. Immunol. 183: 1065-1073.
39. Banz, A., A. Peixoto, C. Pontoux, C. Cordier, B. Rocha, and M. Papiernik. 2003. A unique subpopulation of CD4+ regulatory T cells controls wasting disease, IL-10 secretion and T cell homeostasis. Eur. J. Immunol. 33: 2419-2428.
40. Brunkow, M. E., E. W. Jeffery, K. A. Hjerrild, B. Paeper, L. B. Clark, S. A. Yasayko, J. E. Wilkinson, D. Galas, S. F. Ziegler, and F. Ramsdell. 2001. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat. Genet. 27: 68-73.
41. Zhang, W., R. Sharma, S. T. Ju, X. S. He, Y. Tao, K. Tsuneyama, Z. Tian, Z. X. Lian, S. M. Fu, and M. E. Gershwin. 2009. Deficiency in regulatory T cells results in development of antimitochondrial antibodies and autoimmune cholangitis. Hepatology 49: 545-552.
42. Bettelli, E., Y. Carrier, W. Gao, T. Korn, T. B. Strom, M. Oukka, H. L. Weiner, and V. K. Kuchroo. 2006. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441: 235-238.
43. Mangan, P. R., L. E. Harrington, D. B. O'Quinn, W. S. Helms, D. C. Bullard, C. O. Elson, R. D. Hatton, S. M. Wahl, T. R. Schoeb, and C. T. Weaver. 2006. Transforming growth factor-beta induces development of the T(H)17 lineage. Nature 441: 231-234.
44. Yang, L., D. E. Anderson, C. Baecher-Allan, W. D. Hastings, E. Bettelli, M. Oukka, V. K. Kuchroo, and D. A. Hafler. 2008. IL-21 and TGF-β are required for differentiation of human T(H)17 cells. Nature 454: 350-352.
45. Park, H., Z. Li, X. O. Yang, S. H. Chang, R. Nurieva, Y. H. Wang, Y. Wang, L. Hood, Z. Zhu, Q. Tian, and C. Dong. 2005. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat. Immunol. 6: 1133-1141.
46. Laurence, A. C. M., C. M. Tato, T. S. Davidson, Y. Kanno, Z. Chen, Z. Yao, R. B. Blank, F. Meylan, R. Siegel, L. Hennighausen, et al. 2007. Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity 26: 371-381.
47. Yang, X. O., R. Nurieva, G. J. Martinez, H. S. Kang, Y. Chung, B. P. Pappu, B. Shah, S. H. Chang, K. S. Schluns, S. S. Watowich, et al. 2008. Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity 29: 44-56.
48. Zhou, L., M. M. Chong, and D. R. Littman. 2009. Plasticity of CD4+ T cell lineage differentiation. Immunity 30: 646-655.
49. Feuerer, M., J. A. Hill, D. Mathis, and C. Benoist. 2009. Foxp3+ regulatory T cells: differentiation, specification, subphenotypes. Nat. Immunol. 10: 689-695.
50. Tsuji, M., N. Komatsu, S. Kawamoto, K. Suzuki, O. Kanagawa, T. Honjo, S. Hori, and S. Fagarasan. 2009. Preferential generation of follicular B helper T cells from Foxp3+ T cells in gut Peyer's patches. Science 323: 1488-1492.
51. Zhou, X., S. L. Bailey-Bucktrout, L. T. Jeker, C. Penaranda, M. Martínez-Llordella, M. Ashby, M. Nakayama, W. Rosenthal, and J. A. Bluestone. 2009. Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo. Nat. Immunol. 10: 1000-1007.
52. Tzachanis, D., G. J. Freeman, N. Hirano, A. A. van Puijenbroek, M. W. Delfs, A. Berezovskaya, L. M. Nadler, and V. A. Boussiotis. 2001. Tob is a negative regulator of activation that is expressed in anergic and quiescent T cells. Nat. Immunol. 2: 1174-1182.
53. Miyazono, K., S. Maeda, and T. Imamura. 2004. Coordinate regulation of cell growth and differentiation by TGF-b superfamily and Runx proteins. Oncogene 23: 4232-4237. (Pubitemid 38758589)
54. Dunn, N. R., C. H. Koonce, D. C. Anderson, A. Islam, E. K. Bikoff, and E. J. Robertson. 2005. Mice exclusively expressing the short isoform of Smad2 develop normally and are viable and fertile. Genes Dev. 19: 152-163.
55. Takenoshita, S., A. Mogi, M. Nagashima, K. Yang, K. Yagi, A. Hanyu, Y. Nagamachi, K. Miyazono, and K. Hagiwara. 1998. Characterization of the MADH2/Smad2 gene, a human Mad homolog responsible for the transforming growth factor-beta and activin signal transduction pathway. Genomics 48: 1-11. (Pubitemid 28110795)
56. Pearce, E. L., A. C. Mullen, G. A. Martins, C. M. Krawczyk, A. S. Hutchins, V. P. Zediak, M. Banica, C. B. DiCioccio, D. A. Gross, C. A. Mao, et al. 2003. Control of effector CD8+ T cell function by the transcription factor Eomesodermin. Science 302: 1041-1043.
57. Sitkovsky, M., D. Lukashev, S. Deaglio, K. Dwyer, S. C. Robson, and A. Ohta. 2008. Adenosine A2A receptor antagonists: blockade of adenosinergic effects and T regulatory cells. Br. J. Pharmacol. 153(Suppl 1): S457-S464.