TNF-α impairs differentiation and function of TGF-β-induced Treg cells in autoimmune diseases through Akt and Smad3 signaling pathway

Journal of Molecular Cell Biology

Volumn 5, Issue 2, 2013, Pages 85-98

  Zhang, Qi ^a   Cui, Feifei ^a   Fang, Lei ^b   Hong, Jian ^b   Zheng, Biao ^b   Zhang, Jingwu Z ^a,b  

^a SHANGHAI JIAO TONG UNIVERSITY SCHOOL OF MEDICINE   (China)

^b GLAXOSMITHKLINE   (China)

Author keywords

autoimmune disease; forkhead box P3 (Foxp3); protein kinase B (Akt); Smad3; transforming growth factor beta (TGF ); tumor necrosis factor alpha (TNF )

Indexed keywords

INTERLEUKIN 2; PROTEIN KINASE B; SMAD3 PROTEIN; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR ALPHA ANTIBODY; TUMOR NECROSIS FACTOR RECEPTOR 2;

ALLERGIC ENCEPHALOMYELITIS; ANIMAL EXPERIMENT; ARTICLE; AUTOIMMUNE DISEASE; BINDING SITE; CELL DIFFERENTIATION; COMPLEX FORMATION; CONTROLLED STUDY; DEMYELINATION; GENETIC TRANSCRIPTION; IN VITRO STUDY; MOUSE; NONHUMAN; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REGULATORY T LYMPHOCYTE; SCID MOUSE; SIGNAL TRANSDUCTION; THERAPY; TRANSCRIPTION INITIATION;

ANIMALS; CELL DIFFERENTIATION; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; ENZYME ACTIVATION; GENE EXPRESSION REGULATION; INFLAMMATION; MICE; MICE, KNOCKOUT; PROTO-ONCOGENE PROTEINS C-AKT; RECEPTORS, TUMOR NECROSIS FACTOR, TYPE II; RESPONSE ELEMENTS; SIGNAL TRANSDUCTION; SMAD3 PROTEIN; T-LYMPHOCYTES, REGULATORY; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84875708261     PISSN: 16742788     EISSN: 17594685     Source Type: Journal    
DOI: 10.1093/jmcb/mjs063     Document Type: Article

References (61)

1. Benson, M.J., Pino-Lagos, K., Rosemblatt, M., et al., (2007). 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, 1765-1774.
2. Bettelli, E., Carrier, Y., Gao, W., et al., (2006). Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441, 235-238.
3. Bluestone, J.A., and Abbas, A.K., (2003). Natural versus adaptive regulatory T cells. Nat. Rev. Immunol. 3, 253-257.
4. Bluestone, J.A., Tang, Q., and Sedwick, C.E., (2008). T regulatory cells in autoimmune diabetes: Past challenges, future prospects. J. Clin. Immunol. 28, 677-684.
5. Boschetti, G., Nancey, S., Sardi, F., et al., (2010). Therapy with anti-TNFalpha antibody enhances number and function of Foxp3(+) regulatory T cells in inflammatory bowel diseases. Inflamm. Bowel Dis. 17, 160-170.
6. Buckner, J.H., (2010). Mechanisms of impaired regulation by CD4(+)CD25(+)FOXP3(+) regulatory T cells in human autoimmune diseases. Nat. Rev. Immunol. 10, 849-859.
7. Caretto, D., Katzman, S.D., Villarino, A.V., et al., (2009). Cutting edge: The Th1 response inhibits the generation of peripheral regulatory T cells. J. Immunol. 184, 30-34.
8. Chen, W., Jin, W., Hardegen, N., et al., (2003). Conversion of peripheral CD4+CD252 nai ?ve T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J. Exp. Med. 198, 1875-1886.
9. Chen, X., Baumel, M., Mannel, D.N., et al., (2007). Interaction of TNF with TNF receptor type 2 promotes expansion and function of mouse CD4+CD25+ T regulatory cells. J. Immunol. 179, 154-161.
10. Chen, Q., Kim, Y.C., Laurence, A., et al., (2011). IL-2 controls the stability of Foxp3 expression in TGF-beta-induced Foxp3+ T cells in vivo. J. Immunol. 186, 6329-6337.
11. Conery, A.R., Cao, Y., Thompson, E.A., et al., (2004). Akt interacts directly with Smad3 to regulate the sensitivity to TGF-beta induced apoptosis. Nat. Cell Biol. 6, 366-372.
12. Crellin, N.K., Garcia, R.V., and Levings, M.K., (2007). Altered activation of AKT is required for the suppressive function of human CD4+CD25+ T regulatory cells. Blood 109, 2014-2022.
13. Curotto de Lafaille, M.A., and Lafaille, J.J., (2009). Natural and adaptive foxp3+ regulatory T cells: More of the same or a division of labor? Immunity 30, 626-635.
14. Curotto de Lafaille, M.A., Kutchukhidze, N., Shen, S., et al., (2008). Adaptive Foxp3+ regulatory T cell-dependent and -independent control of allergic inflammation. Immunity 29, 114-126.
15. Duarte, J.H., Zelenay, S., Bergman, M.L., et al., (2009). Natural Treg cells spontaneously differentiate into pathogenic helper cells in lymphopenic conditions. Eur. J. Immunol. 39, 948-955.
16. Edwards, A.J., and Pender, S.L., (2011). Histone deacetylase inhibitors and their potential role in inflammatory bowel diseases. Biochem. Soc. Trans. 39, 1092-1095.
17. Ehrenstein, M.R., Evans, J.G., Singh, A., et al., (2004). Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFalpha therapy. J. Exp. Med. 200, 277-285.
18. Floess, S., Freyer, J., Siewert, C., et al., (2007). Epigenetic control of the foxp3 locus in regulatory T cells. PLoS Biol. 5, e38.
19. Furtado, G.C., Curotto de Lafaille, M.A., Kutchukhidze, N., et al., (2002). Interleukin 2 signaling is required for CD4(+) regulatory T cell function. J. Exp. Med. 196, 851-857.
20. Grinberg-Bleyer, Y., Saadoun, D., Baeyens, A., et al., (2010). Pathogenic T cells have a paradoxical protective effect in murine autoimmune diabetes by boosting Tregs. J. Clin. Invest. 120, 4558-4568.
21. Haas, J., Hug, A., Viehover, A., et al., (2005). Reduced suppressive effect of CD4+CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis. Eur. J. Immunol. 35, 3343-3352.
22. Haribhai, D., Lin, W., Edwards, B., et al., (2009). A central role for induced regulatory T cells in tolerance induction in experimental colitis. J. Immunol. 182, 3461-3468.
23. Jordan, M.S., Boesteanu, A., Reed, A.J., et al., (2001). Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nat. Immunol. 2, 301-306.
24. Kohm, A.P., Carpentier, P.A., Anger, H.A., et al., (2002). Cutting edge: CD4+CD25+ regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis. J. Immunol. 169, 4712-4716.
25. Kruglov, A.A., Kuchmiy, A., Grivennikov, S.I., et al., (2008). Physiological functions of tumor necrosis factor and the consequences of its pathologic overexpression or blockade: Mouse models. Cytokine Growth Factor Rev. 19, 231-244.
26. La Cava, A., (2008). Tregs are regulated by cytokines: Implications for autoimmunity. Autoimmun. Rev. 8, 83-87.
27. Liu, X., Sun, Y., Constantinescu, S.N., et al., (1997). Transforming growth factor beta-induced phosphorylation of Smad3 is required for growth inhibition and transcriptional induction in epithelial cells. Proc. Natl Acad. Sci. USA 94, 10669-10674.
28. Liu, Y., Teige, I., Birnir, B., et al., (2006). Neuron-mediated generation of regulatory T cells from encephalitogenic T cells suppresses EAE. Nat. Med. 12, 518-525.
29. Liu, V.C., Wong, L.Y., Jang, T., et al., (2007). Tumor evasion of the immune system by converting CD4+CD252 T cells into CD4+CD25+ T regulatory cells: Role of tumor-derived TGF-beta. J. Immunol. 178, 2883-2892.
30. Mantel, P.Y., Ouaked, N., Ruckert, B., et al., (2006). Molecular mechanisms underlying FOXP3 induction in human T cells. J. Immunol. 176, 3593-3602.
31. Mantel, P.Y., Kuipers, H., Boyman, O., et al., (2007). GATA3-driven Th2 responses inhibit TGF-beta1-induced FOXP3 expression and the formation of regulatory T cells. PLoS Biol. 5, e329.
32. Martinez, G.J., Zhang, Z., Chung, Y., et al., (2009). Smad3 differentially regulates the induction of regulatory and inflammatory T cell differentiation. J. Biol. Chem. 284, 35283-35286.
33. Massague, J., and Wotton, D., (2000). Transcriptional control by the TGF-beta/Smad signaling system. EMBO J. 19, 1745-1754.
34. Mucida, D., Kutchukhidze, N., Erazo, A., et al., (2005). Oral tolerance in the absence of naturally occurring Tregs. J. Clin. Invest. 115, 1923-1933.
35. Nadkarni, S., Mauri, C., and Ehrenstein, M.R., (2007). Anti-TNF-Alpha therapy induces a distinct regulatory T cell population in patients with rheumatoid arthritis via TGF-beta. J. Exp. Med. 204, 33-39.
36. Ouaked, N., Mantel, P.Y., Bassin, C., et al., (2009). Regulation of the foxp3 gene by the Th1 cytokines: The role of IL-27-induced STAT1. J. Immunol. 182, 1041-1049.
37. Polansky, J.K., Kretschmer, K., Freyer, J., et al., (2008). DNA methylation controls Foxp3 gene expression. Eur. J. Immunol. 38, 1654-1663.
38. Read, S.,Malmstrom, V., and Powrie, F., (2000). Cytotoxic T lymphocyte-Associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation. J. Exp. Med. 192, 295-302.
39. Remy, I., Montmarquette, A., and Michnick, S.W., (2004). PKB/Akt modulates TGF-beta signalling through a direct interaction with Smad3. Nat. Cell Biol. 6, 358-365.
40. Ricciardelli, I., Lindley, K.J., Londei, M., et al., (2008). Anti tumour necrosis-Alpha therapy increases the number of FOXP3 regulatory T cells in children affected by Crohn's disease. Immunology 125, 178-183.
41. Rubtsov, Y.P., Niec, R.E., Josefowicz, S., et al., (2010). Stability of the regulatory T cell lineage in vivo. Science 329, 1667-1671.
42. Ryba, M., Marek, N., Hak, L., et al., (2011). Anti-TNF rescue CD4+Foxp3+ regulatory T cells in patients with type 1 diabetes from effects mediated by TNF. Cytokine 55, 353-361.
43. Sakaguchi, S., Yamaguchi, T., Nomura, T., et al., (2008). Regulatory T cells and immune tolerance. Cell 133, 775-787.
44. Samon, J.B., Champhekar, A., Minter, L.M., et al., (2008). Notch1 and TGFbeta1 cooperatively regulate Foxp3 expression and the maintenance of peripheral regulatory T cells. Blood 112, 1813-1821.
45. Sauer, S., Bruno, L., Hertweck, A., et al., (2008). T cell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR. Proc. Natl Acad. Sci. USA 105, 7797-7802.
46. Selvaraj, R.K., and Geiger, T.L., (2008). Mitigation of experimental allergic encephalomyelitis by TGF-beta induced Foxp3+ regulatory T lymphocytes through the induction of anergy and infectious tolerance. J. Immunol. 180, 2830-2838.
47. Shi, Y., Wang, Y.F., Jayaraman, L., et al., (1998). Crystal structure of a Smad MH1 domain bound to DNA: Insights on DNA binding in TGF-beta signaling. Cell 94, 585-594.
48. Song, K., Wang, H., Krebs, T.L., et al., (2006). Novel roles of Akt and mTOR in suppressing TGF-beta/ALK5-mediated Smad3 activation. EMBO J. 25, 58-69.
49. Thompson, L.J., Valladao, A.C., and Ziegler, S.F., (2011). Cutting edge: De novo induction of functional Foxp3+ regulatory CD4 T cells in response to tissue-restricted self antigen. J. Immunol. 186, 4551-4555.
50. Tone, Y., Furuuchi, K., Kojima, Y., et al., (2008). Smad3 and NFAT cooperate to induce Foxp3 expression through its enhancer. Nat. Immunol. 9, 194-202.
51. Valencia, X., Stephens, G., Goldbach-Mansky, R., et al., (2006). TNF downmodulates the function of human CD4+CD25hi T-regulatory cells. Blood 108, 253-261.
52. Vang, K.B., Yang, J., Mahmud, S.A., et al., (2008). IL-2, -7, and -15, but not thymic stromal lymphopoeitin, redundantly govern CD4+Foxp3+ regulatory T cell development. J. Immunol. 181, 3285-3290.
53. Wajant, H., Pfizenmaier, K., and Scheurich, P., (2003). Tumor necrosis factor signaling. Cell Death Differ. 10, 45-65.
54. Wan, Y.Y., and Flavell, R.A., (2007). Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression. Nature 445, 766-770.
55. Wang, Z., Hong, J., Sun, W., et al., (2006). Role of IFN-gamma in induction of Foxp3 and conversion of CD4+ CD252 T cells to CD4+ Tregs. J. Clin. Invest. 116, 2434-2441.
56. Weber, S.E., Harbertson, J., Godebu, E., et al., (2006). Adaptive islet-specific regulatory CD4 T cells control autoimmune diabetes and mediate the disappearance of pathogenic Th1 cells in vivo. J. Immunol. 176, 4730-4739.
57. Wei, J., Duramad, O., Perng, O.A., et al., (2007). Antagonistic nature of T helper 1/2 developmental programs in opposing peripheral induction of Foxp3+ regulatory T cells. Proc. Natl Acad. Sci. USA 104, 18169-18174.
58. Xu, L., Kitani, A., Fuss, I., et al., (2007). Cutting edge: Regulatory T cells induce CD4+CD252Foxp32 T cells or are self-induced to become Th17 cells in the absence of exogenous TGF-beta. J. Immunol. 178, 6725-6729.
59. Zheng, S.G., Wang, J.H., Koss, M.N., et al., (2004). CD4+ and CD8+ regulatory T cells generated ex vivo with IL-2 and TGF-beta suppress a stimulatory graft-versus-host disease with a lupus-like syndrome. J. Immunol. 172, 1531-1539.
60. Zheng, S.G., Wang, J., and Horwitz, D.A., (2008). Cutting edge: Foxp3+CD4+CD25+ regulatory T cells induced by IL-2 and TGF-beta are resistant to Th17 conversion by IL-6. J. Immunol. 180, 7112-7116.
61. Zhou, X., Bailey-Bucktrout, S.L., Jeker, L.T., et al., (2009). Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo. Nat. Immunol. 10, 1000-1007.