TNF receptor-associated factor (TRAF) signaling network in CD4+ T-Lymphocytes

Tohoku Journal of Experimental Medicine

Volumn 236, Issue 2, 2015, Pages 139-154

  So, Takanori ^a   Nagashima, Hiroyuki ^a   Ishii, Naoto ^a  

^a TOHOKU UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

Author keywords

CD4+ T cells; Signalosome; T cell biology; TNFR; TRAF

Indexed keywords

INTERLEUKIN 1; INTERLEUKIN 2; INTERLEUKIN 6; T LYMPHOCYTE RECEPTOR; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 1; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 2; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 3; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 4; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 5; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 6; CYTOKINE; LYMPHOCYTE ANTIGEN RECEPTOR; TUMOR NECROSIS FACTOR RECEPTOR;

CD4+ T LYMPHOCYTE; CELL SURVIVAL; CELLULAR IMMUNITY; HUMAN; LYMPHOCYTE ACTIVATION; LYMPHOCYTE DIFFERENTIATION; MOLECULAR MECHANICS; NONHUMAN; PROTEIN FUNCTION; PROTEIN STRUCTURE; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE SUBPOPULATION; ANIMAL; PHYSIOLOGY;

ANIMALS; CD4-POSITIVE T-LYMPHOCYTES; CYTOKINES; HUMANS; RECEPTORS, ANTIGEN, T-CELL; RECEPTORS, TUMOR NECROSIS FACTOR; SIGNAL TRANSDUCTION;

EID: 84935846818     PISSN: 00408727     EISSN: 13493329     Source Type: Journal    
DOI: 10.1620/tjem.236.139     Document Type: Review

References (142)

1. Aizawa, S., Nakano, H., Ishida, T., Horie, R., Nagai, M., Ito, K., Yagita, H., Okumura, K., Inoue, J. & Watanabe, T. (1997) Tumor necrosis factor receptor-associated factor (TRAF) 5 and TRAF2 are involved in CD30-mediated NFkappaB activation. J. Biol. Chem., 272, 2042-2045.
2. Akiba, H., Nakano, H., Nishinaka, S., Shindo, M., Kobata, T., Atsuta, M., Morimoto, C., Ware, C.F., Malinin, N.L., Wallach, D., Yagita, H. & Okumura, K. (1998) CD27, a member of the tumor necrosis factor receptor superfamily, activates NFkappaB and stress-activated protein kinase/c-Jun N-terminal kinase via TRAF2, TRAF5, and NF-kappaB-inducing kinase. J. Biol. Chem., 273, 13353-13358.
3. Arch, R.H. & Thompson, C.B. (1998) 4-1BB and Ox40 are members of a tumor necrosis factor (TNF)-nerve growth factor receptor subfamily that bind TNF receptor-associated factors and activate nuclear factor kappaB. Mol. Cell. Biol., 18, 558-565.
4. Basu, R., Whitley, S.K., Bhaumik, S., Zindl, C.L., Schoeb, T.R., Benveniste, E.N., Pear, W.S., Hatton, R.D. & Weaver, C.T. (2015) IL-1 signaling modulates activation of STAT transcription factors to antagonize retinoic acid signaling and control the TH17 cell-iTreg cell balance. Nat. Immunol., 16, 286-295.
5. Boraschi, D. & Tagliabue, A. (2013) The interleukin-1 receptor family. Semin. Immunol., 25, 394-407.
6. Boucher, L.M., Marengere, L.E., Lu, Y., Thukral, S. & Mak, T.W. (1997) Binding sites of cytoplasmic effectors TRAF1, 2, and 3 on CD30 and other members of the TNF receptor superfamily. Biochem. Biophys. Res. Commun., 233, 592-600.
7. Bryce, P.J., Oyoshi, M.K., Kawamoto, S., Oettgen, H.C. & Tsitsikov, E.N. (2006) TRAF1 regulates Th2 differentiation, allergic inflammation and nuclear localization of the Th2 transcription factor, NIP 45. Int. Immunol., 18, 101-111.
8. Cabal-Hierro, L., Rodriguez, M., Artime, N., Iglesias, J., Ugarte, L., Prado, M.A. & Lazo, P.S. (2014) TRAF-mediated modulation of NF-kB AND JNK activation by TNFR 2. Cell. Signal., 26, 2658-2666.
9. Cannons, J.L., Choi, Y. & Watts, T.H. (2000) Role of TNF receptor-associated factor 2 and p38 mitogen-activated protein kinase activation during 4-1BB-dependent immune response. J. Immunol., 165, 6193-6204.
10. Cannons, J.L., Hoeflich, K.P., Woodgett, J.R. & Watts, T.H. (1999) Role of the stress kinase pathway in signaling via the T cell costimulatory receptor 4-1BB. J. Immunol., 163, 2990-2998.
11. Cao, Z., Xiong, J., Takeuchi, M., Kurama, T. & Goeddel, D.V. (1996) TRAF6 is a signal transducer for interleukin-1. Nature, 383, 443-446.
12. Cejas, P.J., Walsh, M.C., Pearce, E.L., Han, D., Harms, G.M., Artis, D., Turka, L.A. & Choi, Y. (2010) TRAF6 inhibits Th17 differentiation and TGF-beta-mediated suppression of IL-2. Blood, 115, 4750-4757.
13. Chang, J.H., Hu, H., Jin, J., Puebla-Osorio, N., Xiao, Y., Gilbert, B.E., Brink, R., Ullrich, S.E. & Sun, S.C. (2014) TRAF3 regulates the effector function of regulatory T cells and humoral immune responses. J. Exp. Med., 211, 137-151.
14. Cherfils-Vicini, J., Vingert, B., Varin, A., Tartour, E., Fridman, W.H., Sautes-Fridman, C., Regnier, C.H. & Cremer, I. (2008) Characterization of immune functions in TRAF4-deficient mice. Immunology, 124, 562-574.
15. Cheung, T.C., Steinberg, M.W., Oborne, L.M., Macauley, M.G., Fukuyama, S., Sanjo, H., D’Souza, C., Norris, P.S., Pfeffer, K., Murphy, K.M., Kronenberg, M., Spear, P.G. & Ware, C.F. (2009) Unconventional ligand activation of herpesvirus entry mediator signals cell survival. Proc. Natl. Acad. Sci. USA, 106, 6244-6249.
16. Chiffoleau, E., Kobayashi, T., Walsh, M.C., King, C.G., Walsh, P.T., Hancock, W.W., Choi, Y. & Turka, L.A. (2003) TNF receptor-associated factor 6 deficiency during hemopoiesis induces Th2-polarized inflammatory disease. J. Immunol., 171, 5751-5759.
17. Chinnaiyan, A.M., O’Rourke, K., Yu, G.L., Lyons, R.H., Garg, M., Duan, D.R., Xing, L., Gentz, R., Ni, J. & Dixit, V.M. (1996) Signal transduction by DR3, a death domain-containing receptor related to TNFR-1 and CD 95. Science, 274, 990-992.
18. Chung, J.Y., Park, Y.C., Ye, H. & Wu, H. (2002) All TRAFs are not created equal: common and distinct molecular mechanisms of TRAF-mediated signal transduction. J. Cell Sci., 115, 679-688.
19. Cote-Sierra, J., Foucras, G., Guo, L., Chiodetti, L., Young, H.A., Hu-Li, J., Zhu, J. & Paul, W.E. (2004) Interleukin 2 plays a central role in Th2 differentiation. Proc. Natl. Acad. Sci. USA, 101, 3880-3885.
20. Croft, M. (2003) Co-stimulatory members of the TNFR family: keys to effective T-cell immunity? Nat. Rev. Immunol., 3, 609-620.
21. Croft, M., So, T., Duan, W. & Soroosh, P. (2009) The significance of OX40 and OX40L to T-cell biology and immune disease. Immunol. Rev., 229, 173-191.
22. Crotty, S. (2011) Follicular helper CD4 T cells (TFH). Annu. Rev. Immunol., 29, 621-663.
23. Duckett, C.S., Gedrich, R.W., Gilfillan, M.C. & Thompson, C.B. (1997) Induction of nuclear factor kappaB by the CD30 receptor is mediated by TRAF1 and TRAF 2. Mol. Cell. Biol., 17, 1535-1542.
24. Endo, Y., Hirahara, K., Iinuma, T., Shinoda, K., Tumes, D.J., Asou, H.K., Matsugae, N., Obata-Ninomiya, K., Yamamoto, H., Motohashi, S., Oboki, K., Nakae, S., Saito, H., Okamoto, Y. & Nakayama, T. (2015) The interleukin-33-p38 kinase axis confers memory T helper 2 cell pathogenicity in the airway. Immunity, 42, 294-308.
25. Esparza, E.M. & Arch, R.H. (2005) Glucocorticoid-induced TNF receptor, a costimulatory receptor on naive and activated T cells, uses TNF receptor-associated factor 2 in a novel fashion as an inhibitor of NF-kappa B activation. J. Immunol., 174, 7875-7882.
26. Esparza, E.M., Lindsten, T., Stockhausen, J.M. & Arch, R.H. (2006) Tumor necrosis factor receptor (TNFR)-associated factor 5 is a critical intermediate of costimulatory signaling pathways triggered by glucocorticoid-induced TNFR in T cells. J. Biol. Chem., 281, 8559-8564.
27. Funakoshi-Tago, M., Tago, K., Hayakawa, M., Tominaga, S., Ohshio, T., Sonoda, Y. & Kasahara, T. (2008) TRAF6 is a critical signal transducer in IL-33 signaling pathway. Cell. Signal., 20, 1679-1686.
28. Gaffen, S.L. (2011) Recent advances in the IL-17 cytokine family. Curr. Opin. Immunol., 23, 613-619.
29. Gardam, S., Sierro, F., Basten, A., Mackay, F. & Brink, R. (2008) TRAF2 and TRAF3 signal adapters act cooperatively to control the maturation and survival signals delivered to B cells by the BAFF receptor. Immunity, 28, 391-401.
30. Garlanda, C., Dinarello, C.A. & Mantovani, A. (2013) The interleukin-1 family: back to the future. Immunity, 39, 1003-1018.
31. Gedrich, R.W., Gilfillan, M.C., Duckett, C.S., Van Dongen, J.L. & Thompson, C.B. (1996) CD30 contains two binding sites with different specificities for members of the tumor necrosis factor receptor-associated factor family of signal transducing proteins. J. Biol. Chem., 271, 12852-12858.
32. Gravestein, L.A., Amsen, D., Boes, M., Calvo, C.R., Kruisbeek, A.M. & Borst, J. (1998) The TNF receptor family member CD27 signals to Jun N-terminal kinase via Traf-2. Eur. J. Immunol., 28, 2208-2216.
33. Ha, H., Han, D. & Choi, Y. (2009) TRAF-mediated TNFR-family signaling. Curr. Protoc. Immunol., Supplement 87, 11.9D.1-11.9D. 19.
34. Hacker, H., Tseng, P.H. & Karin, M. (2011) Expanding TRAF function: TRAF3 as a tri-faced immune regulator. Nat. Rev. Immunol., 11, 457-468.
35. Harlin, H., Podack, E., Boothby, M. & Alegre, M.L. (2002) TCRindependent CD30 signaling selectively induces IL-13 production via a TNF receptor-associated factor/p38 mitogen-activated protein kinase-dependent mechanism. J. Immunol., 169, 2451-2459.
36. Hayden, M.S. & Ghosh, S. (2014) Regulation of NF-kappaB by TNF family cytokines. Semin. Immunol., 26, 253-266.
37. Heldin, C.H., Miyazono, K. & ten Dijke, P. (1997) TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature, 390, 465-471.
38. Hsu, H., Solovyev, I., Colombero, A., Elliott, R., Kelley, M. & Boyle, W.J. (1997) ATAR, a novel tumor necrosis factor receptor family member, signals through TRAF2 and TRAF 5. J. Biol. Chem., 272, 13471-13474.
39. Inoue, J., Ishida, T., Tsukamoto, N., Kobayashi, N., Naito, A., Azuma, S. & Yamamoto, T. (2000) Tumor necrosis factor receptor-associated factor (TRAF) family: adapter proteins that mediate cytokine signaling. Exp. Cell Res., 254, 14-24.
40. Jang, I.K., Lee, Z.H., Kim, Y.J., Kim, S.H. & Kwon, B.S. (1998) Human 4-1BB (CD137) signals are mediated by TRAF2 and activate nuclear factor-kappa B. Biochem. Biophys. Res. Commun., 242, 613-620.
41. Kanamaru, F., Youngnak, P., Hashiguchi, M., Nishioka, T., Takahashi, T., Sakaguchi, S., Ishikawa, I. & Azuma, M. (2004) Costimulation via glucocorticoid-induced TNF receptor in both conventional and CD25+ regulatory CD4+ T cells. J. Immunol., 172, 7306-7314.
42. Karin, M. & Gallagher, E. (2009) TNFR signaling: ubiquitinconjugated TRAFfic signals control stop-and-go for MAPK signaling complexes. Immunol. Rev., 228, 225-240.
43. Kawai, T. & Akira, S. (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat. Immunol., 11, 373-384.
44. Kawamata, S., Hori, T., Imura, A., Takaori-Kondo, A. & Uchiyama, T. (1998) Activation of OX40 signal transduction pathways leads to tumor necrosis factor receptor-associated factor (TRAF) 2-and TRAF5-mediated NF-kappaB activation. J. Biol. Chem., 273, 5808-5814.
45. Kimura, A. & Kishimoto, T. (2010) IL-6: regulator of Treg/Th17 balance. Eur. J. Immunol., 40, 1830-1835.
46. King, C.G., Kobayashi, T., Cejas, P.J., Kim, T., Yoon, K., Kim, G.K., Chiffoleau, E., Hickman, S.P., Walsh, P.T., Turka, L.A. & Choi, Y. (2006) TRAF6 is a T cell-intrinsic negative regulator required for the maintenance of immune homeostasis. Nat. Med., 12, 1088-1092.
47. Kojima, H., Takeuchi, M., Ohta, T., Nishida, Y., Arai, N., Ikeda, M., Ikegami, H. & Kurimoto, M. (1998) Interleukin-18 activates the IRAK-TRAF6 pathway in mouse EL-4 cells. Biochem. Biophys. Res. Commun., 244, 183-186.
48. Korn, T., Bettelli, E., Oukka, M. & Kuchroo, V.K. (2009) IL-17 and Th17 Cells. Annu. Rev. Immunol., 27, 485-517.
49. Kraus, Z.J., Haring, J.S. & Bishop, G.A. (2008) TNF receptorassociated factor 5 is required for optimal T cell expansion and survival in response to infection. J. Immunol., 181, 7800-7809.
50. Krogsgaard, M. & Davis, M.M. (2005) How T cells ‘see’ antigen. Nat. Immunol., 6, 239-245.
51. Kwon, B., Yu, K.Y., Ni, J., Yu, G.L., Jang, I.K., Kim, Y.J., Xing, L., Liu, D., Wang, S.X. & Kwon, B.S. (1999) Identification of a novel activation-inducible protein of the tumor necrosis factor receptor superfamily and its ligand. J. Biol. Chem., 274, 6056-6061.
52. Laurence, A., Tato, C.M., Davidson, T.S., Kanno, Y., Chen, Z., Yao, Z., Blank, R.B., Meylan, F., Siegel, R., Hennighausen, L., Shevach, E.M. & O’Shea, J.J. (2007) Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity, 26, 371-381.
53. Lee, S.Y., Park, C.G. & Choi, Y. (1996) T cell receptor-dependent cell death of T cell hybridomas mediated by the CD30 cytoplasmic domain in association with tumor necrosis factor receptor-associated factors. J. Exp. Med., 183, 669-674.
54. Lee, H.W., Park, S.J., Choi, B.K., Kim, H.H., Nam, K.O. & Kwon, B.S. (2002) 4-1BB promotes the survival of CD8+ T lymphocytes by increasing expression of Bcl-xL and Bfl-1. J. Immunol., 169, 4882-4888.
55. Li, M.O., Wan, Y.Y., Sanjabi, S., Robertson, A.K. & Flavell, R.A. (2006) Transforming growth factor-beta regulation of immune responses. Annu. Rev. Immunol., 24, 99-146.
56. Liao, W., Lin, J.X. & Leonard, W.J. (2013) Interleukin-2 at the crossroads of effector responses, tolerance, and immunotherapy. Immunity, 38, 13-25.
57. Liao, G., Zhang, M., Harhaj, E.W. & Sun, S.C. (2004) Regulation of the NF-kappaB-inducing kinase by tumor necrosis factor receptor-associated factor 3-induced degradation. J. Biol. Chem., 279, 26243-26250.
58. Lin, W.J., Su, Y.W., Lu, Y.C., Hao, Z., Chio, I.I., Chen, N.J., Brustle, A., Li, W.Y. & Mak, T.W. (2011) Crucial role for TNF receptor-associated factor 2 (TRAF2) in regulating NFkappaB2 signaling that contributes to autoimmunity. Proc. Natl. Acad. Sci. USA, 108, 18354-18359.
59. Littman, D.R. & Rudensky, A.Y. (2010) Th17 and regulatory T cells in mediating and restraining inflammation. Cell, 140, 845-858.
60. Lomaga, M.A., Yeh, W.C., Sarosi, I., Duncan, G.S., Furlonger, C., Ho, A., Morony, S., Capparelli, C., Van, G., Kaufman, S., van der Heiden, A., Itie, A., Wakeham, A., Khoo, W., Sasaki, T., et al. (1999) TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling. Genes. Dev., 13, 1015-1024.
61. Maezawa, Y., Nakajima, H., Suzuki, K., Tamachi, T., Ikeda, K., Inoue, J., Saito, Y. & Iwamoto, I. (2006) Involvement of TNF receptor-associated factor 6 in IL-25 receptor signaling. J. Immunol., 176, 1013-1018.
62. Manna, S.K. & Ramesh, G.T. (2005) Interleukin-8 induces nuclear transcription factor-kappaB through a TRAF6-dependent pathway. J. Biol. Chem., 280, 7010-7021.
63. Marsters, S.A., Ayres, T.M., Skubatch, M., Gray, C.L., Rothe, M. & Ashkenazi, A. (1997) Herpesvirus entry mediator, a member of the tumor necrosis factor receptor (TNFR) family, interacts with members of the TNFR-associated factor family and activates the transcription factors NF-kappaB and AP-1. J. Biol. Chem., 272, 14029-14032.
64. McPherson, A.J., Snell, L.M., Mak, T.W. & Watts, T.H. (2012) Opposing roles for TRAF1 in the alternative versus classical NF-kappaB pathway in T cells. J. Biol. Chem., 287, 23010-23019.
65. Meads, M.B., Li, Z.W. & Dalton, W.S. (2010) A novel TNF receptor-associated factor 6 binding domain mediates NF-kappa B signaling by the common cytokine receptor beta subunit. J. Immunol., 185, 1606-1615.
66. Motegi, H., Shimo, Y., Akiyama, T. & Inoue, J. (2011) TRAF6 negatively regulates the Jak1-Erk pathway in interleukin-2 signaling. Genes Cells, 16, 179-189.
67. Murphy, K.M. & Reiner, S.L. (2002) The lineage decisions of helper T cells. Nat. Rev. Immunol., 2, 933-944.
68. Murphy, K., Travers, P. & Walport, M. (2007) Janeway’s immunobiology, 7th ed., Garland Science, Taylor & Francis Group, LLC, pp. 344-345.
69. Murray, S.E., Polesso, F., Rowe, A.M., Basak, S., Koguchi, Y., Toren, K.G., Hoffmann, A. & Parker, D.C. (2011) NF-kappaB-inducing kinase plays an essential T cell-intrinsic role in graft-versus-host disease and lethal autoimmunity in mice. J. Clin. Invest., 121, 4775-4786.
70. Muto, G., Kotani, H., Kondo, T., Morita, R., Tsuruta, S., Kobayashi, T., Luche, H., Fehling, H.J., Walsh, M., Choi, Y. & Yoshimura, A. (2013) TRAF6 is essential for maintenance of regulatory T cells that suppress Th2 type autoimmunity. PLoS One, 8, e74639.
71. Nagashima, H., Okuyama, Y., Asao, A., Kawabe, T., Yamaki, S., Nakano, H., Croft, M., Ishii, N. & So, T. (2014) The adaptor TRAF5 limits the differentiation of inflammatory CD4(+) T cells by antagonizing signaling via the receptor for IL-6. Nat. Immunol., 15, 449-456.
72. Naito, A., Azuma, S., Tanaka, S., Miyazaki, T., Takaki, S., Takatsu, K., Nakao, K., Nakamura, K., Katsuki, M., Yamamoto, T. & Inoue, J. (1999) Severe osteopetrosis, defective interleukin-1 signalling and lymph node organogenesis in TRAF6-deficient mice. Genes Cells, 4, 353-362.
73. Nakanishi, K., Yoshimoto, T., Tsutsui, H. & Okamura, H. (2001) Interleukin-18 regulates both Th1 and Th2 responses. Annu. Rev. Immunol., 19, 423-474.
74. Nakano, H., Sakon, S., Koseki, H., Takemori, T., Tada, K., Matsumoto, M., Munechika, E., Sakai, T., Shirasawa, T., Akiba, H., Kobata, T., Santee, S.M., Ware, C.F., Rennert, P.D., Taniguchi, M., et al. (1999) Targeted disruption of Traf5 gene causes defects in CD40-and CD27-mediated lymphocyte activation. Proc. Natl. Acad. Sci. USA, 96, 9803-9808.
75. Nakayama, T. & Yamashita, M. (2010) The TCR-mediated signaling pathways that control the direction of helper T cell differentiation. Semin. Immunol., 22, 303-309.
76. Nam, K.O., Kang, H., Shin, S.M., Cho, K.H., Kwon, B., Kwon, B.S., Kim, S.J. & Lee, H.W. (2005) Cross-linking of 4-1BB activates TCR-signaling pathways in CD8+ T lymphocytes. J. Immunol., 174, 1898-1905.
77. Nguyen, L.T., Duncan, G.S., Mirtsos, C., Ng, M., Speiser, D.E., Shahinian, A., Marino, M.W., Mak, T.W., Ohashi, P.S. & Yeh, W.C. (1999) TRAF2 deficiency results in hyperactivity of certain TNFR1 signals and impairment of CD40-mediated responses. Immunity, 11, 379-389.
78. Oeckinghaus, A., Wegener, E., Welteke, V., Ferch, U., Arslan, S.C., Ruland, J., Scheidereit, C. & Krappmann, D. (2007) Malt1 ubiquitination triggers NF-kappaB signaling upon T-cell activation. EMBO J., 26, 4634-4645.
79. Oh, H. & Ghosh, S. (2013) NF-kappaB: roles and regulation in different CD4(+) T-cell subsets. Immunol. Rev., 252, 41-51.
80. Park, Y.C., Burkitt, V., Villa, A.R., Tong, L. & Wu, H. (1999) Structural basis for self-association and receptor recognition of human TRAF 2. Nature, 398, 533-538.
81. Park, Y.C., Ye, H., Hsia, C., Segal, D., Rich, R.L., Liou, H.C., Myszka, D.G. & Wu, H. (2000) A novel mechanism of TRAF signaling revealed by structural and functional analyses of the TRADD-TRAF2 interaction. Cell, 101, 777-787.
82. Pearce, E.L., Walsh, M.C., Cejas, P.J., Harms, G.M., Shen, H., Wang, L.S., Jones, R.G. & Choi, Y. (2009) Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature, 460, 103-107.
83. Piao, J.H., Hasegawa, M., Heissig, B., Hattori, K., Takeda, K., Iwakura, Y., Okumura, K., Inohara, N. & Nakano, H. (2011) Tumor necrosis factor receptor-associated factor (TRAF) 2 controls homeostasis of the colon to prevent spontaneous development of murine inflammatory bowel disease. J. Biol. Chem., 286, 17879-17888.
84. Pobezinskaya, Y.L., Choksi, S., Morgan, M.J., Cao, X. & Liu, Z.G. (2011) The adaptor protein TRADD is essential for TNF-like ligand 1A/death receptor 3 signaling. J. Immunol., 186, 5212-5216.
85. Prell, R.A., Evans, D.E., Thalhofer, C., Shi, T., Funatake, C. & Weinberg, A.D. (2003) OX40-mediated memory T cell generation is TNF receptor-associated factor 2 dependent. J. Immunol., 171, 5997-6005.
86. Regnier, C.H., Masson, R., Kedinger, V., Textoris, J., Stoll, I., Chenard, M.P., Dierich, A., Tomasetto, C. & Rio, M.C. (2002) Impaired neural tube closure, axial skeleton malformations, and tracheal ring disruption in TRAF4-deficient mice. Proc. Natl. Acad. Sci. USA, 99, 5585-5590.
87. Rothe, M., Wong, S.C., Henzel, W.J. & Goeddel, D.V. (1994) A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor. Cell, 78, 681-692.
88. Rowe, A.M., Murray, S.E., Raue, H.P., Koguchi, Y., Slifka, M.K. & Parker, D.C. (2013) A cell-intrinsic requirement for NF-kappaB-inducing kinase in CD4 and CD8 T cell memory. J. Immunol., 191, 3663-3672.
89. Sabbagh, L., Andreeva, D., Laramee, G.D., Oussa, N.A., Lew, D., Bisson, N., Soumounou, Y., Pawson, T. & Watts, T.H. (2013) Leukocyte-specific protein 1 links TNF receptor-associated factor 1 to survival signaling downstream of 4-1BB in T cells. J. Leukoc. Biol., 93, 713-721.
90. Sabbagh, L., Pulle, G., Liu, Y., Tsitsikov, E.N. & Watts, T.H. (2008) ERK-dependent Bim modulation downstream of the4-1BBTRAF1 signaling axis is a critical mediator of CD8 T cell survival in vivo. J. Immunol., 180, 8093-8101.
91. Sabbagh, L., Srokowski, C.C., Pulle, G., Snell, L.M., Sedgmen, B.J., Liu, Y., Tsitsikov, E.N. & Watts, T.H. (2006) A critical role for TNF receptor-associated factor 1 and Bim down-regulation in CD8 memory T cell survival. Proc. Natl. Acad. Sci. USA, 103, 18703-18708.
92. Sakaguchi, S., Yamaguchi, T., Nomura, T. & Ono, M. (2008) Regulatory T cells and immune tolerance. Cell, 133, 775-787.
93. Saoulli, K., Lee, S.Y., Cannons, J.L., Yeh, W.C., Santana, A., Goldstein, M.D., Bangia, N., DeBenedette, M.A., Mak, T.W., Choi, Y. & Watts, T.H. (1998) CD28-independent, TRAF2-dependent costimulation of resting T cells by 4-1BB ligand. J. Exp. Med., 187, 1849-1862.
94. Shiels, H., Li, X., Schumacker, P.T., Maltepe, E., Padrid, P.A., Sperling, A., Thompson, C.B. & Lindsten, T. (2000) TRAF4 deficiency leads to tracheal malformation with resulting alterations in air flow to the lungs. Am. J. Pathol., 157, 679-688.
95. Shimo, Y., Yanai, H., Ohshima, D., Qin, J., Motegi, H., Maruyama, Y., Hori, S., Inoue, J. & Akiyama, T. (2011) TRAF6 directs commitment to regulatory T cells in thymocytes. Genes Cells, 16, 437-447.
96. Silke, J. & Brink, R. (2010) Regulation of TNFRSF and innate immune signalling complexes by TRAFs and cIAPs. Cell Death Differ., 17, 35-45.
97. Simoncic, P.D., Lee-Loy, A., Barber, D.L., Tremblay, M.L. & McGlade, C.J. (2002) The T cell protein tyrosine phosphatase is a negative regulator of janus family kinases 1 and 3. Curr. Biol., 12, 446-453.
98. Smith-Garvin, J.E., Koretzky, G.A. & Jordan, M.S. (2009) T cell activation. Annu. Rev. Immunol., 27, 591-619.
99. Snell, L.M., McPherson, A.J., Lin, G.H., Sakaguchi, S., Pandolfi, P.P., Riccardi, C. & Watts, T.H. (2010) CD8 T cell-intrinsic GITR is required for T cell clonal expansion and mouse survival following severe influenza infection. J. Immunol., 185, 7223-7234.
100. So, T., Choi, H. & Croft, M. (2011a) OX40 complexes with phosphoinositide3-kinase and protein kinase B (PKB) to augment TCR-dependent PKB signaling. J. Immunol., 186, 3547-3555.
101. So, T. & Croft, M. (2012) Regulation of the PKCtheta-NF-kappaB Axis in T Lymphocytes by the Tumor Necrosis Factor Receptor Family Member OX 40. Front. Immunol., 3, 133.
102. So, T. & Croft, M. (2013) Regulation of PI-3-Kinase and Akt Signaling in T Lymphocytes and Other Cells by TNFR Family Molecules. Front. Immunol., 4, 139.
103. So, T., Salek-Ardakani, S., Nakano, H., Ware, C.F. & Croft, M. (2004) TNF receptor-associated factor 5 limits the induction of Th2 immune responses. J. Immunol., 172, 4292-4297.
104. So, T., Soroosh, P., Eun, S.Y., Altman, A. & Croft, M. (2011b) Antigen-independent signalosome of CARMA1, PKCtheta, and TNF receptor-associated factor 2 (TRAF2) determines NF-kappaB signaling in T cells. Proc. Natl. Acad. Sci. USA, 108, 2903-2908.
105. Sorrentino, A., Thakur, N., Grimsby, S., Marcusson, A., von Bulow, V., Schuster, N., Zhang, S., Heldin, C.H. & Landstrom, M. (2008) The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner. Nat. Cell Biol., 10, 1199-1207.
106. Stahl, N., Farruggella, T.J., Boulton, T.G., Zhong, Z., Darnell, J.E. Jr. & Yancopoulos, G.D. (1995) Choice of STATs and other substrates specified by modular tyrosine-based motifs in cytokine receptors. Science, 267, 1349-1353.
107. Sugamura, K., Asao, H., Kondo, M., Tanaka, N., Ishii, N., Ohbo, K., Nakamura, M. & Takeshita, T. (1996) The interleukin-2 receptor gamma chain: its role in the multiple cytokine receptor complexes and T cell development in XSCID. Annu. Rev. Immunol., 14, 179-205.
108. Sun, L., Deng, L., Ea, C.K., Xia, Z.P. & Chen, Z.J. (2004) The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. Mol. Cell, 14, 289-301.
109. Taga, T. & Kishimoto, T. (1997) Gp130 and the interleukin-6 family of cytokines. Annu. Rev. Immunol., 15, 797-819.
110. Takeda, K., Kaisho, T. & Akira, S. (2003) Toll-like receptors. Annu. Rev. Immunol., 21, 335-376.
111. Takeda, K., Noguchi, T., Naguro, I. & Ichijo, H. (2008) Apoptosis signal-regulating kinase1 in stress and immune response. Annu. Rev. Pharmacol. Toxicol., 48, 199-225.
112. Thome, M. (2008) Multifunctional roles for MALT1 in T-cell activation. Nat. Rev. Immunol., 8, 495-500.
113. Thome, M., Charton, J.E., Pelzer, C. & Hailfinger, S. (2010) Antigen receptor signaling to NF-kappaB via CARMA1, BCL10, and MALT 1. Cold Spring Harb. Perspect. Biol., 2, a003004.
114. Tsitsikov, E.N., Laouini, D., Dunn, I.F., Sannikova, T.Y., Davidson, L., Alt, F.W. & Geha, R.S. (2001) TRAF1 is a negative regulator of TNF signaling. enhanced TNF signaling in TRAF1-deficient mice. Immunity, 15, 647-657.
115. Vallabhapurapu, S., Matsuzawa, A., Zhang, W., Tseng, P.H., Keats, J.J., Wang, H., Vignali, D.A., Bergsagel, P.L. & Karin, M. (2008) Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-kappaB signaling. Nat. Immunol., 9, 1364-1370.
116. Varfolomeev, E., Blankenship, J.W., Wayson, S.M., Fedorova, A.V., Kayagaki, N., Garg, P., Zobel, K., Dynek, J.N., Elliott, L.O., Wallweber, H.J., Flygare, J.A., Fairbrother, W.J., Deshayes, K., Dixit, V.M. & Vucic, D. (2007) IAP antagonists induce autoubiquitination of c-IAPs, NF-kappaB activation, and TNFalphadependent apoptosis. Cell, 131, 669-681.
117. Varfolomeev, E., Goncharov, T., Maecker, H., Zobel, K., Komuves, L.G., Deshayes, K. & Vucic, D. (2012) Cellular inhibitors of apoptosis are global regulators of NF-kappaB and MAPK activation by members of the TNF family of receptors. Sci. Signal., 5, ra22.
118. Villanueva, J.E., Malle, E.K., Gardam, S., Silveira, P.A., Zammit, N.W., Walters, S.N., Brink, R. & Grey, S.T. (2015) TRAF2 regulates peripheral CD8+ T-cell and NKT-cell homeostasis by modulating sensitivity to IL-15. Eur. J. Immunol., 45, 1820-1831.
119. Walsh, M.C., Pearce, E.L., Cejas, P.J., Lee, J., Wang, L.S. & Choi, Y. (2014) IL-18 synergizes with IL-7 to drive slow proliferation of naive CD8 T cells by costimulating self-peptide-mediated TCR signals. J. Immunol., 193, 3992-4001.
120. Wang, C., McPherson, A.J., Jones, R.B., Kawamura, K.S., Lin, G.H., Lang, P.A., Ambagala, T., Pellegrini, M., Calzascia, T., Aidarus, N., Elford, A.R., Yue, F.Y., Kremmer, E., Kovacs, C.M., Benko, E., et al. (2012) Loss of the signaling adaptor TRAF1 causes CD8+ T cell dysregulation during human and murine chronic infection. J. Exp. Med., 209, 77-91.
121. Wang, C., Wen, T., Routy, J.P., Bernard, N.F., Sekaly, R.P. & Watts, T.H. (2007) 4-1BBL induces TNF receptor-associated factor 1-dependent Bim modulation in human T cells and is a critical component in the costimulation-dependent rescue of functionally impaired HIV-specific CD8 T cells. J. Immunol., 179, 8252-8263.
122. Watts, T.H. (2005) TNF/TNFR family members in costimulation of T cell responses. Annu. Rev. Immunol., 23, 23-68.
123. Weaver, C.T., Hatton, R.D., Mangan, P.R. & Harrington, L.E. (2007) IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu. Rev. Immunol., 25, 821-852.
124. Xiao, X., Balasubramanian, S., Liu, W., Chu, X., Wang, H., Taparowsky, E.J., Fu, Y.X., Choi, Y., Walsh, M.C. & Li, X.C. (2012) OX40 signaling favors the induction of T(H)9 cells and airway inflammation. Nat. Immunol., 13, 981-990.
125. Xie, Y.F., Cui, Y.B., Hui, X.W., Wang, L., Ma, X.L., Chen, H., Wang, X. & Huang, B.R. (2012) Interaction of IFNlambdaR1 with TRAF6 regulates NF-kappaB activation and IFNlambdaR1 stability. J. Cell. Biochem., 113, 3371-3379.
126. Xie, P., Kraus, Z.J., Stunz, L.L., Liu, Y. & Bishop, G.A. (2011) TNF receptor-associated factor 3 is required for T cell-mediated immunity and TCR/CD28 signaling. J. Immunol., 186, 143-155.
127. Xu, Y., Cheng, G. & Baltimore, D. (1996) Targeted disruption of TRAF3 leads to postnatal lethality and defective T-dependent immune responses. Immunity, 5, 407-415.
128. Yamamoto, H., Kishimoto, T. & Minamoto, S. (1998) NF-kappaB activation in CD27 signaling: involvement of TNF receptorassociated factors in its signaling and identification of functional region of CD 27. J. Immunol., 161, 4753-4759.
129. Yamane, H. & Paul, W.E. (2012) Cytokines of the gamma(c) family control CD4+ T cell differentiation and function. Nat. Immunol., 13, 1037-1044.
130. Yamane, H. & Paul, W.E. (2013) Early signaling events that underlie fate decisions of naive CD4(+) T cells toward distinct T-helper cell subsets. Immunol. Rev., 252, 12-23.
131. Yamashita, M., Fatyol, K., Jin, C., Wang, X., Liu, Z. & Zhang, Y.E. (2008) TRAF6 mediates Smad-independent activation of JNK and p38 by TGF-beta. Mol. Cell, 31, 918-924.
132. Yang, C.H., Murti, A., Pfeffer, S.R., Fan, M., Du, Z. & Pfeffer, L.M. (2008) The role of TRAF2 binding to the type I interferon receptor in alternative NF kappaB activation and antiviral response. J. Biol. Chem., 283, 14309-14316.
133. Ye, H., Arron, J.R., Lamothe, B., Cirilli, M., Kobayashi, T., Shevde, N.K., Segal, D., Dzivenu, O.K., Vologodskaia, M., Yim, M., Du, K., Singh, S., Pike, J.W., Darnay, B.G., Choi, Y., et al. (2002) Distinct molecular mechanism for initiating TRAF6 signalling. Nature, 418, 443-447.
134. Ye, H., Park, Y.C., Kreishman, M., Kieff, E. & Wu, H. (1999) The structural basis for the recognition of diverse receptor sequences by TRAF 2. Mol. Cell, 4, 321-330.
135. Yeh, W.C., Shahinian, A., Speiser, D., Kraunus, J., Billia, F., Wakeham, A., de la Pompa, J.L., Ferrick, D., Hum, B., Iscove, N., Ohashi, P., Rothe, M., Goeddel, D.V. & Mak, T.W. (1997) Early lethality, functional NF-kappaB activation, and increased sensitivity to TNF-induced cell death in TRAF2-deficient mice. Immunity, 7, 715-725.
136. Yi, Z., Lin, W.W., Stunz, L.L. & Bishop, G.A. (2014a) The adaptor TRAF3 restrains the lineage determination of thymic regulatory T cells by modulating signaling via the receptor for IL-2. Nat. Immunol., 15, 866-874.
137. Yi, Z., Stunz, L.L., Lin, W.W. & Bishop, G.A. (2014b) TRAF3 regulates homeostasis of CD8+ central memory T cells. PLoS One, 9, e102120.
138. Yokosuka, T. & Saito, T. (2009) Dynamic regulation of T-cell costimulation through TCR-CD28 microclusters. Immunol. Rev., 229, 27-40.
139. Yoshimura, A., Naka, T. & Kubo, M. (2007) SOCS proteins, cytokine signalling and immune regulation. Nat. Rev. Immunol., 7, 454-465.
140. Zarnegar, B.J., Wang, Y., Mahoney, D.J., Dempsey, P.W., Cheung, H.H., He, J., Shiba, T., Yang, X., Yeh, W.C., Mak, T.W., Korneluk, R.G. & Cheng, G. (2008) Noncanonical NF-kappaB activation requires coordinated assembly of a regulatory complex of the adaptors cIAP1, cIAP2, TRAF2 and TRAF3 and the kinase NIK. Nat. Immunol., 9, 1371-1378.
141. Zheng, C., Kabaleeswaran, V., Wang, Y., Cheng, G. & Wu, H. (2010) Crystal structures of the TRAF2: cIAP2 and the TRAF1: TRAF2: cIAP2 complexes: affinity, specificity, and regulation. Mol. Cell, 38, 101-113.
142. Zhu, J., Yamane, H. & Paul, W.E. (2010) Differentiation of effector CD4 T cell populations. Annu. Rev. Immunol., 28, 445-489.