Suppression of Th2 and Tfh immune reactions by Nr4a receptors in mature T reg cells

Journal of Experimental Medicine

Volumn 212, Issue 10, 2015, Pages 1623-1640

  Sekiya, Takashi ^a   Kondo, Taisuke ^a   Shichita, Takashi ^a   Morita, Rimpei ^a   Ichinose, Hiroshi ^b   Yoshimura, Akihiko ^a,c  

^a KEIO UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^b TOKYO INSTITUTE OF TECHNOLOGY   (Japan)

^c JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

IMMUNOGLOBULIN E; IMMUNOGLOBULIN G1; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 21; INTERLEUKIN 4; NUCLEAR PROTEIN; NUCLEAR RECEPTOR NR4A3; NUCLEAR RECEPTOR NUR77; NUCLEAR RECEPTOR RELATED FACTOR 1; PROTEIN; PROTEIN IKZF4; TRANSCRIPTION FACTOR FOXP3; UNCLASSIFIED DRUG; CARRIER PROTEIN; DNA BINDING PROTEIN; FORKHEAD TRANSCRIPTION FACTOR; FOXP3 PROTEIN, MOUSE; NERVE PROTEIN; NR4A1 PROTEIN, MOUSE; NR4A2 PROTEIN, MOUSE; NR4A3 PROTEIN, MOUSE; STEROID RECEPTOR; THYROID HORMONE RECEPTOR; ZFPN1A4 PROTEIN, MOUSE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CELL FUNCTION; CELL LINEAGE; CONTROLLED STUDY; ENHANCER REGION; FOLLICULAR HELPER T LYMPHOCYTE; GENE DELETION; GENE EXPRESSION; HISTONE MODIFICATION; IMMUNITY; IMMUNOPATHOLOGY; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE SUBPOPULATION; TH2 CELL; TRANSCRIPTION REGULATION; ANIMAL; C57BL MOUSE; GENE EXPRESSION REGULATION; GENETIC TRANSCRIPTION; GENETICS; HELPER CELL; IMMUNOLOGY; KNOCKOUT MOUSE; METABOLISM;

ANIMALS; CARRIER PROTEINS; DNA-BINDING PROTEINS; FORKHEAD TRANSCRIPTION FACTORS; GENE EXPRESSION REGULATION; INTERLEUKIN-4; MICE, INBRED C57BL; MICE, KNOCKOUT; NERVE TISSUE PROTEINS; NUCLEAR RECEPTOR SUBFAMILY 4, GROUP A, MEMBER 1; NUCLEAR RECEPTOR SUBFAMILY 4, GROUP A, MEMBER 2; RECEPTORS, STEROID; RECEPTORS, THYROID HORMONE; T-LYMPHOCYTES, HELPER-INDUCER; T-LYMPHOCYTES, REGULATORY; TH2 CELLS; TRANSCRIPTION, GENETIC;

EID: 84959544872     PISSN: 00221007     EISSN: 15409538     Source Type: Journal    
DOI: 10.1084/jem.20142088     Document Type: Article

References (52)

1. Abbas, A.K., S. Urioste, T.L. Collins, and W.H. Boom. 1990. Heterogeneity of helper/inducer T lymphocytes. IV. Stimulation of resting and activated B cells by Th1 and Th2 clones. J. Immunol. 144:2031-2037.
2. Agarwal, S., and A. Rao. 1998. Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation. Immunity. 9: 765-775. http://dx.doi.org/10.1016/S1074-7613(00)80642-1
3. Bailey-Bucktrout, S.L., M. Martinez-Llordella, X. Zhou, B. Anthony, W. Rosenthal, H. Luche, H.J. Fehling, and J.A. Bluestone. 2013. Selfantigen-driven activation induces instability of regulatory T cells during an inflammatory autoimmune response. Immunity. 39: 949-962. http://dx.doi.org/10.1016/j.immuni.2013.10.016
4. Chung, Y., S. Tanaka, F. Chu, R.I. Nurieva, G.J. Martinez, S. Rawal, Y.H. Wang, H. Lim, J.M. Reynolds, X.H. Zhou, et al. 2011. Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions. Nat. Med. 17: 983-988. http://dx.doi.org/10.1038/nm.2426
5. Crotty, S. 2011. Follicular helper CD4 T cells (TFH). Annu. Rev. Immunol. 29: 621-663. http://dx.doi.org/10.1146/annurev-immunol-031210-101400
6. Floess, S., J. Freyer, C. Siewert, U. Baron, S. Olek, J. Polansky, K. Schlawe, H.D. Chang, T. Bopp, E. Schmitt, et al. 2007. Epigenetic control of the foxp3 locus in regulatory T cells. PLoS Biol. 5:e38. http://dx.doi .org/10.1371/journal.pbio.0050038
7. 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. http://dx.doi.org/10.1038/ni904
8. Fontenot, J.D., J.P. Rasmussen, M.A. Gavin, and A.Y. Rudensky. 2005. A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nat. Immunol. 6: 1142-1151. http://dx.doi.org/10.1038/ni1263
9. Gavin, M.A., J.P. Rasmussen, J.D. Fontenot, V. Vasta, V.C. Manganiello, J.A. Beavo, and A.Y. Rudensky. 2007. Foxp3-dependent programme of regulatory T-cell differentiation. Nature. 445: 771-775. http://dx.doi .org/10.1038/nature05543
10. Hamers, A.A., R.N. Hanna, H. Nowyhed, C.C. Hedrick, and C.J. de Vries. 2013. NR4A nuclear receptors in immunity and atherosclerosis. Curr. Opin. Lipidol. 24:381-385.
11. 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. http://dx.doi.org/10.1016/j.immuni.2007.09.010
12. Hori, S., T. Nomura, and S. Sakaguchi. 2003. Control of regulatory T cell development by the transcription factor Foxp3. Science. 299: 1057-1061. http://dx.doi.org/10.1126/science.1079490
13. Iikuni, N., E.V. Lourenço, B.H. Hahn, and A. La Cava. 2009. Cutting edge:regulatory T cells directly suppress B cells in systemic lupus erythematosus. J. Immunol. 183: 1518-1522. http://dx.doi.org/10.4049/jimmunol .0901163
14. Kadkhodaei, B., T. Ito, E. Joodmardi, B. Mattsson, C. Rouillard, M. Carta, S. Muramatsu, C. Sumi-Ichinose, T. Nomura, D. Metzger, et al. 2009. Nurr1 is required for maintenance of maturing and adult midbrain dopamine neurons. J. Neurosci. 29: 15923-15932. http://dx.doi.org/10.1523/JNEUROSCI.3910-09.2009
15. Khattri, R., T. Cox, S.A. Yasayko, and F. Ramsdell. 2003. An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat. Immunol. 4: 337-342. http://dx.doi.org/10.1038/ni909
16. Kim, H.P., and W.J. Leonard. 2007. CREB/ATF-dependent T cell receptorinduced FoxP3 gene expression: a role for DNA methylation. J. Exp. Med. 204: 1543-1551. http://dx.doi.org/10.1084/jem.20070109
17. Kim, J.M., J.P. Rasmussen, and A.Y. Rudensky. 2007. Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat. Immunol. 8: 191-197. http://dx.doi.org/10.1038/ni1428
18. King, C. 2009. New insights into the differentiation and function of T follicular helper cells. Nat. Rev. Immunol. 9: 757-766. http://dx.doi.org/10.1038/nri2644
19. Komatsu, N., K. Okamoto, S. Sawa, T. Nakashima, M. Oh-hora, T. Kodama, S. Tanaka, J.A. Bluestone, and H. Takayanagi. 2014. Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis. Nat. Med. 20: 62-68. http://dx.doi.org/10.1038/nm.3432
20. Levine, A.G., A. Arvey, W. Jin, and A.Y. Rudensky. 2014. Continuous requirement for the TCR in regulatory T cell function. Nat. Immunol. 15: 1070-1078. http://dx.doi.org/10.1038/ni.3004
21. Lim, H.W., P. Hillsamer, and C.H. Kim. 2004. Regulatory T cells can migrate to follicles upon T cell activation and suppress GC-Th cells and GC-Th cell-driven B cell responses. J. Clin. Invest. 114: 1640-1649. http://dx.doi .org/10.1172/JCI200422325
22. Lin, W., D. Haribhai, L.M. Relland, N. Truong, M.R. Carlson, C.B. Williams, and T.A. Chatila. 2007. Regulatory T cell development in the absence of functional Foxp3. Nat. Immunol. 8: 359-368. http://dx.doi.org/10.1038/ni1445
23. Linterman, M.A., W. Pierson, S.K. Lee, A. Kallies, S. Kawamoto, T.F. Rayner, M. Srivastava, D.P. Divekar, L. Beaton, J.J. Hogan, et al. 2011. Foxp3+ follicular regulatory T cells control the germinal center response. Nat. Med. 17: 975-982. http://dx.doi.org/10.1038/nm.2425
24. Lloyd, C.M., and C.M. Hawrylowicz. 2009. Regulatory T cells in asthma. Immunity. 31: 438-449. http://dx.doi.org/10.1016/j.immuni.2009.08.007
25. Lu, K.T., Y. Kanno, J.L. Cannons, R. Handon, P. Bible, A.G. Elkahloun, S.M. Anderson, L. Wei, H. Sun, J.J. O'Shea, and P.L. Schwartzberg. 2011. Functional and epigenetic studies reveal multistep differentiation and plasticity of in vitro-generated and in vivo-derived follicular T helper cells. Immunity. 35: 622-632. http://dx.doi.org/10.1016/j.immuni.2011.07.015
26. Luche, H., O. Weber, T. Nageswara Rao, C. Blum, and H.J. Fehling. 2007. Faithful activation of an extra-bright red fluorescent protein in "knockin" Cre-reporter mice ideally suited for lineage tracing studies. Eur. J. Immunol. 37: 43-53. http://dx.doi.org/10.1002/eji.200636745
27. Luo, C.T., and M.O. Li. 2013. Transcriptional control of regulatory T cell development and function. Trends Immunol. 34: 531-539. http://dx.doi .org/10.1016/j.it.2013.08.003
28. Miyao, T., S. Floess, R. Setoguchi, H. Luche, H.J. Fehling, H. Waldmann, J. Huehn, and S. Hori. 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. http://dx.doi.org/10.1016/j.immuni.2011.12.012
29. Miyara, M., and S. Sakaguchi. 2007. Natural regulatory T cells: mechanisms of suppression. Trends Mol. Med. 13: 108-116. http://dx.doi.org/10.1016/j.molmed.2007.01.003
30. Moran, A.E., K.L. Holzapfel, Y. Xing, N.R. Cunningham, J.S. Maltzman, J. Punt, and K.A. Hogquist. 2011. T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouse. J. Exp. Med. 208: 1279-1289. http://dx.doi.org/10.1084/jem.20110308
31. Murai, M., O. Turovskaya, G. Kim, R. Madan, C.L. Karp, H. Cheroutre, and M. Kronenberg. 2009. Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis. Nat. Immunol. 10: 1178-1184. http://dx.doi.org/10.1038/ni.1791
32. Muto, G., H. Kotani, T. Kondo, R. Morita, S. Tsuruta, T. Kobayashi, H. Luche, H.J. Fehling, M. Walsh, Y. Choi, and A. Yoshimura. 2013. TRAF6 is essential for maintenance of regulatory T cells that suppress Th2 type autoimmunity. PLoS ONE. 8:e74639. http://dx.doi.org/10.1371/journal .pone.0074639
33. Ouyang, W., W. Liao, C.T. Luo, N. Yin, M. Huse, M.V. Kim, M. Peng, P. Chan, Q. Ma, Y. Mo, et al. 2012. Novel Foxo1-dependent transcriptional programs control T(reg) cell function. Nature. 491: 554-559. http://dx.doi.org/10.1038/nature11581
34. Pan, F., H. Yu, E.V. Dang, J. Barbi, X. Pan, J.F. Grosso, D. Jinasena, S.M. Sharma, E.M. McCadden, D. Getnet, et al. 2009. Eos mediates Foxp3-dependent gene silencing in CD4+ regulatory T cells. Science. 325: 1142-1146. http://dx.doi.org/10.1126/science.1176077
35. Rubtsov, Y.P., J.P. Rasmussen, E.Y. Chi, J. Fontenot, L. Castelli, X. Ye, P. Treuting, L. Siewe, A. Roers, W.R. Henderson Jr., et al. 2008. Regulatory T cellderived interleukin-10 limits inflammation at environmental interfaces. Immunity. 28: 546-558. http://dx.doi.org/10.1016/j.immuni.2008.02.017
36. Rubtsov, Y.P., R.E. Niec, S. Josefowicz, L. Li, J. Darce, D. Mathis, C. Benoist, and A.Y. Rudensky. 2010. Stability of the regulatory T cell lineage in vivo. Science. 329: 1667-1671. http://dx.doi.org/10.1126/science.1191996
37. Saijo, K., B. Winner, C.T. Carson, J.G. Collier, L. Boyer, M.G. Rosenfeld, F.H. Gage, and C.K. Glass. 2009. A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell. 137: 47-59. http://dx.doi.org/10.1016/j.cell.2009.01.038
38. Sakaguchi, S., T. Yamaguchi, T. Nomura, and M. Ono. 2008. Regulatory T cells and immune tolerance. Cell. 133: 775-787. http://dx.doi.org/10.1016/j.cell.2008.05.009
39. Seibler, J., B. Zevnik, B. Küter-Luks, S. Andreas, H. Kern, T. Hennek, A. Rode, C. Heimann, N. Faust, G. Kauselmann, et al. 2003. Rapid generation of inducible mouse mutants. Nucleic Acids Res. 31:e12. http://dx.doi.org/10.1093/nar/gng012
40. Sekiya, T., I. Kashiwagi, N. Inoue, R. Morita, S. Hori, H. Waldmann, A.Y. Rudensky, H. Ichinose, D. Metzger, P. Chambon, and A. Yoshimura. 2011. The nuclear orphan receptor Nr4a2 induces Foxp3 and regulates differentiation of CD4+ T cells. Nat. Commun. 2:269. http://dx.doi.org/ 10.1038/ncomms1272
41. Sekiya, T., I. Kashiwagi, R. Yoshida, T. Fukaya, R. Morita, A. Kimura, H. Ichinose, D. Metzger, P. Chambon, and A. Yoshimura. 2013. Nr4a receptors are essential for thymic regulatory T cell development and immune homeostasis. Nat. Immunol. 14: 230-237. http://dx.doi.org/10.1038/ni.2520
42. Setoguchi, R., S. Hori, T. Takahashi, and S. Sakaguchi. 2005. Homeostatic maintenance of natural Foxp3+ CD25+ CD4+ regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization. J. Exp. Med. 201: 723-735. http://dx.doi.org/10.1084/jem.20041982
43. Takahashi, T., Y. Kuniyasu, M. Toda, N. Sakaguchi, M. Itoh, M. Iwata, J. Shimizu, and S. Sakaguchi. 1998. Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state. Int. Immunol. 10: 1969-1980. http://dx.doi.org/10.1093/intimm/10.12.1969
44. Thornton, A.M., and E.M. Shevach. 1998. CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J. Exp. Med. 188: 287-296. http://dx.doi.org/ 10.1084/jem.188.2.287
45. Thornton, A.M., and E.M. Shevach. 2000. Suppressor effector function of CD4+CD25+ immunoregulatory T cells is antigen nonspecific. J. Immunol. 164: 183-190. http://dx.doi.org/10.4049/jimmunol.164.1.183
46. 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. http://dx.doi.org/10.1126/science.1169152
47. Vignali, D.A., L.W. Collison, and C.J. Workman. 2008. How regulatory T cells work. Nat. Rev. Immunol. 8: 523-532. http://dx.doi.org/10.1038/nri2343
48. Wehner, J.R., K. Fox-Talbot, M.K. Halushka, C. Ellis, A.A. Zachary, and W.M. Baldwin III. 2010. B cells and plasma cells in coronaries of chronically rejected cardiac transplants. Transplantation. 89: 1141-1148. http://dx.doi.org/10.1097/TP.0b013e3181d3f271
49. 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. http://dx.doi.org/10.1016/j.immuni.2008.12.009
50. Wing, K., Y. Onishi, P. Prieto-Martin, T. Yamaguchi, M. Miyara, Z. Fehervari, T. Nomura, and S. Sakaguchi. 2008. CTLA-4 control over Foxp3+ regulatory T cell function. Science. 322: 271-275. http://dx.doi.org/10.1126/science.1160062
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. http://dx.doi.org/10.1038/ni.1774
52. Zhu, J., J. Cote-Sierra, L. Guo, and W.E. Paul. 2003. Stat5 activation plays a critical role in Th2 differentiation. Immunity. 19: 739-748. http://dx .doi.org/10.1016/S1074-7613(03)00292-9