TRAF6 Is Essential for Maintenance of Regulatory T Cells That Suppress Th2 Type Autoimmunity

PLoS ONE

Volumn 8, Issue 9, 2013, Pages

  Muto, Go ^a   Kotani, Hitoshi ^a   Kondo, Taisuke ^a   Morita, Rimpei ^a   Tsuruta, Sanae ^a   Kobayashi, Takashi ^b,c   Luche, Hervé ^d   Fehling, Hans Joerg ^d   Walsh, Matthew ^e   Choi, Yongwon ^e   Yoshimura, Akihiko ^a  

^a KEIO UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^b JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

^c OITA UNIVERSITY   (Japan)

^d UNIVERSITY HOSPITAL ULM   (Germany)

^e UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CRE RECOMBINASE; IMMUNOGLOBULIN E ANTIBODY; INTERLEUKIN 6; TRANSCRIPTION FACTOR FOXP3; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 6;

ADOPTIVE TRANSFER; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTHRITIS; ARTICLE; AUTOIMMUNITY; CELL COUNT; CELL FATE; COLITIS; CONTROLLED STUDY; CYTOKINE PRODUCTION; FEMALE; HOMEOSTASIS; HYPER IGE SYNDROME; IN VITRO STUDY; LYMPHADENOPATHY; MALE; MOUSE; NONHUMAN; PROTEIN DEFICIENCY; PROTEIN FUNCTION; REGULATORY T LYMPHOCYTE; SKIN ALLERGY; TH2 CELL;

ANIMALS; AUTOIMMUNITY; CELL PROLIFERATION; FEMALE; FORKHEAD TRANSCRIPTION FACTORS; INTEGRASES; INTERLEUKIN-2; LYMPHOCYTE ACTIVATION; MICE; MICE, KNOCKOUT; PHENOTYPE; STAT5 TRANSCRIPTION FACTOR; T-LYMPHOCYTES, REGULATORY; TH2 CELLS; TNF RECEPTOR-ASSOCIATED FACTOR 6;

EID: 84884161974     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0074639     Document Type: Article

References (37)

1. Sakaguchi S, Yamaguchi T, Nomura T, Ono M, (2008) Regulatory T cells and immune tolerance. Cell 133: 775-787. doi:10.1016/j.cell.2008.05.009. PubMed: 18510923.
2. Wan YY, Flavell RA, (2007) Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression. Nature 445: 766-770. doi:10.1038/nature05479. PubMed: 17220876.
3. Lee HM, Bautista JL, Hsieh CS, (2011) Thymic and peripheral differentiation of regulatory T cells. Adv Immunol 112: 25-71. doi:10.1016/B978-0-12-387827-4.00002-4. PubMed: 22118406.
4. Ohkura N, Hamaguchi M, Sakaguchi S, (2011) FOXP3+ regulatory T cells: control of FOXP3 expression by pharmacological agents. Trends Pharmacol Sci 32: 158-166. doi:10.1016/j.tips.2010.12.004. PubMed: 21237521.
5. Takimoto T, Wakabayashi Y, Sekiya T, Inoue N, Morita R, et al. (2010) Smad2 and Smad3 are redundantly essential for the TGF-beta-mediated regulation of regulatory T plasticity and Th1 development. J Immunol 185: 842-855. doi:10.4049/jimmunol.0904100. PubMed: 20548029.
6. Sekiya T, Kashiwagi I, Yoshida R, Fukaya T, Morita R, et al. (2013) Nr4a receptors are essential for thymic regulatory T cell development and immune homeostasis. Nat Immunol 14: 230-237. doi:10.1038/ni.2520. PubMed: 23334790.
7. Wing JB, Sakaguchi S, (2012) Multiple treg suppressive modules and their adaptability. Frontiers in immunology 3. p. 178.
8. Komatsu N, Mariotti-Ferrandiz ME, Wang Y, Malissen B, Waldmann H, et al. (2009) Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity. Proc Natl Acad Sci U S A 106: 1903-1908. doi:10.1073/pnas.0811556106. PubMed: 19174509.
9. Tsuji M, Komatsu N, Kawamoto S, Suzuki K, Kanagawa O, et al. (2009) Preferential generation of follicular B helper T cells from Foxp3+ T cells in gut Peyer's patches. Science 323: 1488-1492. doi:10.1126/science.1169152. PubMed: 19286559.
10. Zhou X, Bailey-Bucktrout SL, Jeker LT, Penaranda C, Martínez-Llordella M, 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. doi:10.1038/ni.1774. PubMed: 19633673.
11. Murai M, Krause P, Cheroutre H, Kronenberg M, (2010) Regulatory T-cell stability and plasticity in mucosal and systemic immune systems. Mucosal Immunol 3: 443-449. doi:10.1038/mi.2010.27. PubMed: 20505662.
12. Miyao T, Floess S, Setoguchi R, Luche H, Fehling HJ, et al. (2012) Plasticity of Foxp3(+) T cells reflects promiscuous Foxp3 expression in conventional T cells but not reprogramming of regulatory T cells. Immunity 36: 262-275. doi:10.1016/j.immuni.2011.12.012. PubMed: 22326580.
13. Takahashi R, Nishimoto S, Muto G, Sekiya T, Tamiya T, et al. (2011) SOCS1 is essential for regulatory T cell functions by preventing loss of Foxp3 expression as well as IFN-{gamma} and IL-17A production. J Exp Med 208: 2055-2067. doi:10.1084/jem.20110428. PubMed: 21893603.
14. Inoue J, Gohda J, Akiyama T, (2007) Characteristics and biological functions of TRAF6. Adv Exp Med Biol 597: 72-79. doi:10.1007/978-0-387-70630-6_6. PubMed: 17633018.
15. Sun L, Deng L, Ea CK, Xia ZP, Chen ZJ, (2004) The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. Mol Cell 14: 289-301. doi:10.1016/S1097-2765(04)00236-9. PubMed: 15125833.
16. King CG, Kobayashi T, Cejas PJ, Kim T, Yoon K, et al. (2006) TRAF6 is a T cell-intrinsic negative regulator required for the maintenance of immune homeostasis. Nat Med 12: 1088-1092. doi:10.1038/nm1449. PubMed: 16921377.
17. Motegi H, Shimo Y, Akiyama T, Inoue J, (2011) TRAF6 negatively regulates the Jak1-Erk pathway in interleukin-2 signaling. Genes Cells Devoted Mol Cell Mech 16: 179-189. doi:10.1111/j.1365-2443.2010.01474.x. PubMed: 21155952.
18. Rubtsov YP, Rasmussen JP, Chi EY, Fontenot J, Castelli L, et al. (2008) Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces. Immunity 28: 546-558. doi:10.1016/j.immuni.2008.02.017. PubMed: 18387831.
19. Sekiya T, Kashiwagi I, Inoue N, Morita R, Hori S, et al. (2011) The nuclear orphan receptor Nr4a2 induces Foxp3 and regulates differentiation of CD4+ T cells. Nat Communications 2: 269. doi:10.1038/ncomms1272. PubMed: 21468021.
20. Kobayashi T, Kim TS, Jacob A, Walsh MC, Kadono Y, et al. (2009) TRAF6 is required for generation of the B-1a B cell compartment as well as T cell-dependent and-independent humoral immune responses. PLOS ONE 4: e4736. doi:10.1371/journal.pone.0004736. PubMed: 19270748.
21. Luche H, Weber O, Nageswara Rao T, Blum C, Fehling HJ, (2007) Faithful activation of an extra-bright red fluorescent protein in "knock-in" Cre-reporter mice ideally suited for lineage tracing studies. Eur J Immunol 37: 43-53. doi:10.1002/eji.200636745. PubMed: 17171761.
22. Chinen T, Komai K, Muto G, Morita R, Inoue N, et al. (2011) Prostaglandin E2 and SOCS1 have a role in intestinal immune tolerance. Nat Commun 2: 190. doi:10.1038/ncomms1181. PubMed: 21304519.
23. Shouda T, Yoshida T, Hanada T, Wakioka T, Oishi M, et al. (2001) Induction of the cytokine signal regulator SOCS3/CIS3 as a therapeutic strategy for treating inflammatory arthritis. J Clin Invest 108: 1781-1788. doi:10.1172/JCI200113568. PubMed: 11748261.
24. Ichiyama K, Sekiya T, Inoue N, Tamiya T, Kashiwagi I, et al. (2011) Transcription factor Smad-independent T helper 17 cell induction by transforming-growth factor-beta is mediated by suppression of eomesodermin. Immunity 34: 741-754. doi:10.1016/j.immuni.2011.02.021. PubMed: 21600798.
25. Beyersdorf N, Ding X, Tietze JK, Hanke T, (2007) Characterization of mouse CD4 T cell subsets defined by expression of KLRG1. Eur J Immunol 37: 3445-3454. doi:10.1002/eji.200737126. PubMed: 18034419.
26. Cejas PJ, Walsh MC, Pearce EL, Han D, Harms GM, et al. (2010) TRAF6 inhibits Th17 differentiation and TGF-beta-mediated suppression of IL-2. Blood 115: 4750-4757. doi:10.1182/blood-2009-09-242768. PubMed: 20351308.
27. Long M, Park SG, Strickland I, Hayden MS, Ghosh S, (2009) Nuclear factor-kappaB modulates regulatory T cell development by directly regulating expression of Foxp3 transcription factor. Immunity 31: 921-931. doi:10.1016/j.immuni.2009.09.022. PubMed: 20064449.
28. Ruan QG, Kameswaran V, Tone Y, Li L, Liou HC, et al. (2009) Development of Foxp3(+) Regulatory T Cells Is Driven by the c-Rel Enhanceosome. Immunity 31: 932-940. doi:10.1016/j.immuni.2009.10.006. PubMed: 20064450.
29. Isomura I, Palmer S, Grumont RJ, Bunting K, Hoyne G, et al. (2009) c-Rel is required for the development of thymic Foxp3(+) CD4 regulatory T cells. J Exp Med 206: 3001-3014. doi:10.1084/jem.20091411. PubMed: 19995950.
30. Visekruna A, Huber M, Hellhund A, Bothur E, Reinhard K, et al. (2010) c-Rel is crucial for the induction of Foxp3(+) regulatory CD4(+) T cells but not T(H)17 cells. Eur J Immunol 40: 671-676. doi:10.1002/eji.200940260. PubMed: 20049877.
31. Liu GW, Zhao Y, (2007) Toll-like receptors and immune regulation: their direct and indirect modulation on regulatory CD4(+) CD25(+) T cells. Immunology 122: 149-156. doi:10.1111/j.1365-2567.2007.02651.x. PubMed: 17848162.
32. Zheng Y, Chaudhry A, Kas A, deRoos P, Kim JM, et al. (2009) Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control T(H)2 responses. Nature 458: 351-356. doi:10.1038/nature07674. PubMed: 19182775.
33. Kitoh A, Ono M, Naoe Y, Ohkura N, Yamaguchi T, et al. (2009) Indispensable role of the Runx1-Cbfbeta transcription complex for in vivo-suppressive function of FoxP3+ regulatory T cells. Immunity 31: 609-620. doi:10.1016/j.immuni.2009.09.003. PubMed: 19800266.
34. Nie H, Zheng Y, Li R, Guo TB, He D, et al. (2013) Phosphorylation of FOXP3 controls regulatory T cell function and is inhibited by TNF-alpha in rheumatoid arthritis. Nat Med 19: 322-328. doi:10.1038/nm.3085. PubMed: 23396208.
35. Dominguez-Villar M, Baecher-Allan CM, Hafler DA, (2011) Identification of T helper type 1-like, Foxp3+ regulatory T cells in human autoimmune disease. Nat Med 17: 673-675. doi:10.1038/nm.2389. PubMed: 21540856.
36. Raychaudhuri S, Thomson BP, Remmers EF, Eyre S, Hinks A, et al. (2009) Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk. Nat Genet 41: 1313-U1376. doi:10.1038/ng.479. PubMed: 19898481.
37. Namjou B, Choi CB, Harley ITW, Alarcón-Riquelme ME, Kelly JA, et al. (2012) Evaluation of TRAF6 in a large multiancestral lupus cohort. Arthritis Rheum 64: 1960-1969. doi:10.1002/art.34361. PubMed: 22231568.