TGFβ signalling in control of T-cell-mediated self-reactivity

Nature Reviews Immunology

Volumn 7, Issue 6, 2007, Pages 443-453

  Rubtsov, Yuri P ^a   Rudensky, Alexander Y ^a  

^a UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD69 ANTIGEN; DNA; HERMES ANTIGEN; INTERLEUKIN 17; INTERLEUKIN 2; INTERLEUKIN 23; INTERLEUKIN 6; RAG1 PROTEIN; RETINOIC ACID RECEPTOR; SMAD PROTEIN; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA RECEPTOR 2; TRANSFORMING GROWTH FACTOR BETA1; TRANSFORMING GROWTH FACTOR BETA2; TRANSFORMING GROWTH FACTOR BETA3;

AUTOIMMUNE DISEASE; CARBOXY TERMINAL SEQUENCE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELLULAR IMMUNITY; COMPLEX FORMATION; DNA BINDING; EXPERIMENTAL MOUSE; GENE EXPRESSION REGULATION; HUMAN; IMMUNOLOGICAL TOLERANCE; IMMUNOREACTIVITY; IMMUNOREGULATION; LYMPHOCYTE DIFFERENTIATION; NATURAL KILLER CELL; NONHUMAN; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN FAMILY; PROTEIN INTERACTION; PROTEIN MOTIF; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; REVIEW; T LYMPHOCYTE; TRANSCRIPTION REGULATION; ANIMAL; AUTOIMMUNITY; CELL DIFFERENTIATION; CYTOLOGY; IMMUNOLOGY; METABOLISM; SIGNAL TRANSDUCTION;

ANIMALS; AUTOIMMUNITY; CELL DIFFERENTIATION; HUMANS; SIGNAL TRANSDUCTION; SMAD PROTEINS; T-LYMPHOCYTES; TRANSFORMING GROWTH FACTOR BETA;

EID: 34249678653     PISSN: 14741733     EISSN: None     Source Type: Journal    
DOI: 10.1038/nri2095     Document Type: Review

References (79)

1. Shi, Y. & Massague, J. Mechanisms of TGF-β signaling from cell membrane to the nucleus. Cell 113, 685-700 (2003).
2. Siegel, P. M. & Massague, J. Cytostatic and apoptotic actions of TGF-β in homeostasis and cancer. Nature Rev. Cancer 3, 807-821 (2003).
3. Kehrl, J. H. et al. Production of transforming growth factor β by human T lymphocytes and its potential role in the regulation of T cell growth. J. Exp. Med. 163, 1037-1050 (1986). This is the first study to implicate an important role for TGFβ1 produced by activated T cells in limiting their proliferation.
4. Li, M. O., Wan, Y. Y., Sanjabi, S., Robertson, A. K. & Flavell, R. A. Transforming growth factor-β regulation of immune responses. Annu. Rev. Immunol. 24, 99-144 (2006).
5. Veldhoen, M. & Stockinger, B. TGFβ1, a 'Jack of all trades': the link with pro-inflammatory IL-17-producing T cells. Trends Immunol. 27, 358-361 (2006).
6. Li, M. O., Sanjabi, S. & Flavell, R. A. Transforming growth factor-β controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and -independent mechanisms. Immunity 25, 455-471 (2006). This study and reference 7 reveal a critical role for TGFβ1 signalling in T cells in preventing fatal early onset autoimmune lesions affecting multiple organs.
7. Marie, J. C., Liggitt, D. & Rudensky A. Y. Cellular mechanisms of fatal early-onset autoimmunity in mice with the T cell-specific targeting of transforming growth factor-β receptor. Immunity 25, 441-454 (2006).
8. - T cells through FoxP3 induction and down-regulation of Smad7. J. Immunol. 172, 5149-5153 (2004).
9. + regulatory T cells. J. Exp. Med. 201, 1061-1067 (2005).
10. + regulatory T cells in immunological tolerance to self and non-self. Nature Immunol. 6, 345-352 (2005).
11. Fontenot, J. D. & Rudensky, A. Y. Molecular aspects of regulatory T cell development. Semin. Immunol. 16, 73-80 (2004).
12. Govinden, R. & Bhoola, K. D. Genealogy, expression, and cellular function of transforming growth factor-β. Pharmacol. Ther. 98, 257-265 (2003).
13. Letterio, J. J. & Roberts, A. B. Regulation of immune responses by TGF-β. Annu. Rev. Immunol. 16, 137-161 (1998).
14. Lagneaux, L., Delforge, A., Dorval, C., Bron, D. & Stryckmans, P. Excessive production of transforming growth factor-β by bone marrow stromal cells in B-cell chronic lymphocytic leukemia inhibits growth of hematopoietic precursors and interleukin-6 production. Blood 82, 2379-2385 (1993).
15. Filer, A., Pitzalis, C. & Buckley C. D. Targeting the stromal microenvironment in chronic inflammation. Curr. Opin. Pharmacol. 6, 394-400 (2006).
16. Kim, S. J. et al. Autoinduction of transforming growth factor β1 is mediated by the AP-1 complex. Mol. Cell. Biol. 10, 1492-1497 (1990).
17. Lee, K. Y. et al. NF-κB and activator protein 1 response elements and the role of histone modifications in IL-1β-induced TGF-β1 gene transcription. J. Immunol. 176, 603-615 (2006).
18. Kim, S. J. et al. Post-transcriptional regulation of the human transforming growth factor-β1 gene. J. Biol. Chem. 267, 13702-13707 (1992).
19. Annes, J. P., Munger, J. S. & Rifkin, D. B. Making sense of latent TGFβ activation. J. Cell. Sci. 116, 217-224 (2003).
20. Nunes, I., Shapiro, R. L. & Rifkin, D. B. Characterization of latent TGF-β activation by murine peritoneal macrophages. J. Immunol. 155, 1450-1459 (1995).
21. Crawford, S. E. et al. Thrombospondin-1 is a major activator of TGF-β1 in vivo. Cell 93, 1159-1170 (1998).
22. 6 binds and activates latent TGFβ1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell 96, 319-328 (1999).
23. 6-mediated activation of latent TGF-β requires the latent TGF-β binding protein-1. J. Cell Biol. 165, 723-734 (2004).
24. Chaudhry, S. S. et al. Fibrillin-1 regulates the bioavailability of TGFβ1. J. Cell. Biol. 176, 355-367 (2007).
25. + T cells. Int. Immunol. 18, 495-503 (2006).
26. Gandhi, R., Anderson, D. E. & Weiner, H. L. Immature human dendritic cells express latency-associated peptide and inhibit T cell activation in a TGF-β-dependent manner. J. Immunol. 178, 4017-4021 (2007).
27. Mitti, P. R. et al. The crystal structure of TGF-β3 and comparison to TGF-β2: implications for receptor binding. Protein Sci. 5, 1261-1271 (1996).
28. Massague, J. TGF-β signal transduction. Ann. Rev. Biochem. 67, 753-791 (1998).
29. Massague, J. How cells read TGF-β signals. Nature Rev. Mol. Cell. Biol. 1, 169-178 (2000).
30. Huse, M. et al. The TGF-β receptor activation process: an inhibitor- to substrate-binding switch. Mol. Cell 8, 671-682 (2001).
31. Massague, J. & Chen, Y.-G. Controlling TGF-β signaling. Genes Dev. 14, 627-644 (2000).
32. Tsukazaki, T., Chiang, T. A., Davison, A. F., Attisano, L. & Wrana, J. T. SARA, a FYVE domain protein that recruits Smad2 to the TGF-β receptor. Cell 95, 779-791 (1998).
33. Inman, G. J., Nicolas, F. J. & Hill, C. S. Nucleocytoplasmic shuttling of Smads 2, 3, and 4 permits sensing of TGF-β receptor activity. Mol. Cell 10, 283-294 (2002).
34. Xu, L., Chen, Y.-G. & Massague, J. Smad2 nuclear import function masked by SARA and unmasked by TGF-β dependent phosphorylation. Nature Cell. Biol. 2, 559-562 (2000).
35. Xu, L., Kang, Y., Col, S. & Massague, J. Smad2 nucleocytoplasmic shuttling by nucleoporins CAN/Nup214 and Nup153 feeds TGF-β signaling complexes in the cytoplasm and nucleus. Mol. Cell 10, 271-282 (2002).
36. Suzuki, C. et al. Smurf1 regulates the inhibitory activity of Smad7 by targeting Smad7 to the plasma membrane. J. Biol. Chem. 277, 39919-39925 (2002).
37. Tajima, Y. et al. Chromosomal region maintenance 1 (CRM1)-dependent nuclear export of Smad ubiquitin regulatory factor 1 (Smurf1) is essential for negative regulation of transforming growth factor-β signaling by Smad7. J. Biol. Chem. 278, 10716-10721 (2003).
38. Di Guglielmo, G. M., Le Roy, C., Davidson, A. F. & Wrana, J. L. Distinct endocytic pathways regulate TGF- β receptor signaling and turnover. Nature Cell Biol. 5, 410-421 (2003).
39. Bhowmick, N. A. et al. Transforming growth factor-?1 mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism. Mol. Biol. Cell 12, 27-36 (2001).
40. Yu, L., Hebert, M. C. & Zhang, Y. E. TGF-β receptor-activated p38 MAP kinase mediated Smad-independent TGF-β responses. EMBO J. 21, 3749-3759 (2002).
41. Itoh, S. et al. Elucidation of Smad requirement in transforming growth factor-β type I receptor-induced responses. J. Biol. Chem. 278, 3751-3761 (2003).
42. Shull, M. M. et al. Targeted disruption of the mouse transforming growth factor-β1 gene results in multifocal inflammatory disease. Nature 359, 693-699 (1992).
43. Nikolich-Zugich, J. Phenotypic and functional stages in the intrathymic development of αβT cells. Immunol. Today 12, 65-70 (1991).
44. - thymocytes. J. Immunol. 146, 3068-3073 (1991).
45. - thymocytes with T cell growth factor-β and tumor necrosis factor-α. J. Immunol. 149, 71-76 (1992).
46. Plum, J., De Smedt, M., Leclercq, G. & Vandekerckhove, B. Influence of TGF-β on murine thymocyte development in fetal thymus organ culture. J. Immunol. 154, 5789-5798 (1995).
47. Mossalayi, M. D. et al. Early human thymocyte proliferation is regulated by an externally controlled autocrine transforming growth factor-β1 mechanism. Blood 85, 3594-35601 (1995).
48. Takahama, Y., Letterio, J. J., Suzuki, H., Farr, A. G. & Singer, A. Early progression of thymocytes along the CD4/CD8 developmental pathway is regulated by a subset of thymic epithelial cells expressing transforming growth factor β. J. Exp. Med. 179, 1495-1506 (1994).
49. Bendelac, A., Savage, P. B. & Teyton, L. The biology of NKT cells. Annu. Rev. Immunol. 25, 297-336 (2007).
50. Benlagha, K., Wei, D. G., Veiga, J., Teyton, L. & Bendelac, A. Characterization of the early stages of thymic NKT cell development. J. Exp. Med. 202, 485-492 (2005).
51. Wolfraim, L. A., Walz, T. M., James, Z., Fernandez, T. & Letterio, J. J. p21Cip1 and p27Kip1 act in synergy to alter the sensitivity of naïve T cells to TGF-β-mediated G1 arrest through modulation of IL-2 responsiveness. J. Immunol. 173, 3093-3102 (2004).
52. Ruegemer, J. J. et al. Regulatory effects of transforming growth factor-β on IL-2- and IL-4-dependent T cell-cycle progression. J. Immunol. 144, 1767-1776 (1994).
53. Genestier, L., Kasibhatla, S., Brunner, T. & Green, D. R. Transforming growth factor β1 inhibits Fas ligand expression and subsequent activation-induced cell death in T cells via downregulation of c-Myc. J. Exp. Med. 189, 231-239 (1999).
54. Nelson, B. H., Martyak, T. P., Thompson, L. J., Moon, J. J. & Wang, T. Uncoupling of promitogenic and antiapoptotic functions of IL-2 by Smad-dependent TGF-β signaling. J. Immunol. 170, 5563-5570 (2003).
55. + T cell survival, division, and IL-2 production: a role for T cell intrinsic Smad3. J. Immunol. 174, 2071-2083 (2005).
56. + regulatory T cells. J. Exp. Med. 201, 737-746 (2005).
57. Gorelik, L. & Flavell, R. A. Abrogation of TGFβ signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease. Immunity 12, 171-181 (2000).
58. Lucas, P. J., Kim, S-J., Melby, S. J. & Gress, R. E. Disruption of T cell homeostasis in mice expressing a T cell-specific dominant negative transforming growth factor βII receptor. J. Exp. Med. 191, 1187-1196 (2000). References 57 and 58 were the first to indicate an important cell-autonomous role for TGFβ1 signalling in T cells by expressing a dominant-negative form of TGFβRII under the control of a T-cell-specific promoter.
59. Gorelik, L., Constant, S. & Flavell, R. A. Mechanism of transforming growth factor-β-induced inhibition of T helper type 1 differentiation. J. Exp. Med. 195, 1499-1505 (2002).
60. Fontenot, J. D. & Rudensky, A. Y. A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3. Nature Immunol. 6, 331-337 (2005).
61. Fontenot, J. D. et al. Regulatory T cell lineage specification by the forkhead transcription factor Foxp3. Immunity 22, 329-341 (2005).
62. + T regulatory cells. Nature Immunol. 4, 337-342 (2003).
63. + regulatory T cells. Nature Immunol. 4, 330-336 (2003).
64. + regulatory T cells from human peripheral blood. J. Immunol. 166, 7282-7289 (2001). The authors of this paper demonstrate that in the presence of high doses of TGFβ1 and stimulation in vitro, conventional T cells acquire the ability to suppress the responses of untreated T cells.
65. - cells.
66. + T regulatory cells. J. Immunol. 178, 4022-4026 (2007).
67. + regulatory T cells and for expansion of these cells. J. Immunol. 178, 2018-2027 (2007).
68. Li, O. M., Wan, Y. Y. & Flavell, R. A. T cell-produced transforming growth factor-β1 controls T cell tolerance and regulates Th1- and Th17-cell differentiation. Immunity 3 May 2007 (doi:10.1016/j.immuni.2007.03.014).
69. + T cells inhibits activity against tumour cells, indicating a possible mechanism of tumour evasion from the immune response.
70. Roncarolo, M. G. et al. Interleukin-10-secreting type 1 regulatory T cells in rodents and humans. Immunol. Rev. 212, 28-50 (2006).
71. Faria, A. M. & Weiner, H. L. Oral tolerance. Immunol. Rev. 206, 232-259 (2005).
72. H-17 cells in the circle of immunity and autoimmunity. Nature Immunol. 8, 345-350 (2007).
73. Weaver, C. T., Hatton R. D., Mangan, P. R. & Harrington, L. E. IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu. Rev. Immunol. 25, 821-852 (2007).
74. Veldhoen, M., Hocking, R. J., Atkins, C. J, Locksley, R. M. & Stockinger, B. TGFβ in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24, 179-189 (2006).
75. H17 and regulatory T cells. Nature 441, 235-238 (2006).
76. + T cells.
77. H17 cells.
78. Gavin, M. A. et al. Foxp3-dependent programme of regulatory T-cell differentiation. Nature 445, 771-775 (2007).
79. Williams, L. M. & Rudensky, A. Y. Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3. Nature Immunol. 8, 277-284 (2007).