The Th17 immune response is controlled by the Rel-RORγ-RORγT transcriptional axis

Journal of Experimental Medicine

Volumn 208, Issue 11, 2011, Pages 2321-2333

  Ruan, Qingguo ^a   Kameswaran, Vasumathi ^a   Zhang, Yan ^a   Zheng, Shijun ^a   Sun, Jing ^a   Wang, Junmei ^b   DeVirgiliis, Jennifer ^a   Liou, Hsiou Chi ^c   Beg, Amer A ^b   Chen, Youhai H ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

^c WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; RETINOID RELATED ORPHAN RECEPTOR GAMMA; SYNAPTOTAGMIN I; TRANSCRIPTION FACTOR REL; TRANSCRIPTION FACTOR RELA;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL DIFFERENTIATION; CONTROLLED STUDY; IMMUNE RESPONSE; MOUSE; NERVE CELL; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; T LYMPHOCYTE; TH17 CELL;

ANIMALS; CELL DIFFERENTIATION; HUMANS; INTERLEUKIN-17; MICE; MICE, INBRED C57BL; MICE, INBRED NOD; MICE, TRANSGENIC; NUCLEAR RECEPTOR SUBFAMILY 1, GROUP F, MEMBER 1; NUCLEAR RECEPTOR SUBFAMILY 1, GROUP F, MEMBER 3; PROMOTER REGIONS, GENETIC; PROTO-ONCOGENE PROTEINS C-REL; SIGNAL TRANSDUCTION; TH17 CELLS; TRANSCRIPTION FACTOR RELA; TRANSCRIPTION, GENETIC;

EID: 80055116357     PISSN: 00221007     EISSN: 15409538     Source Type: Journal    
DOI: 10.1084/jem.20110462     Document Type: Article

References (43)

1. Barnes, P.J., and M. Karin. 1997. Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N. Engl. J. Med. 336:1066-1071. http://dx.doi.org/10.1056/NEJM199704103361506.
2. Beg, A.A., and D. Baltimore. 1996. An essential role for NF-kappaB in preventing TNF-alpha-induced cell death. Science. 274:782-784. http://dx.doi.org/10.1126/science.274.5288.782.
3. Bettelli, E., Y. Carrier, W. Gao, T. Korn, T.B. Strom, M. Oukka, H.L. Weiner, and V.K. Kuchroo. 2006. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 441:235-238. http://dx.doi.org/10.1038/nature04753.
4. Brownell, E., B. Mathieson, H.A. Young, J. Keller, J.N. Ihle, and N.R. Rice. 1987. Detection of c-rel-related transcripts in mouse hematopoietic tissues, fractionated lymphocyte populations, and cell lines. Mol. Cell. Biol. 7:1304-1309.
5. Bunting, K., S. Rao, K. Hardy, D. Woltring, G.S. Denyer, J. Wang, S. Gerondakis, and M.F. Shannon. 2007. Genome-wide analysis of gene expression in T cells to identify targets of the NF-kappa B transcription factor c-Rel. J. Immunol. 178:7097-7109.
6. Carmody, R.J., Q. Ruan, H.-C. Liou, and Y.H. Chen. 2007. Essential roles of c-Rel in Toll-like receptor-induced interleukin-23 p19 gene expression in dendritic cells. J. Immunol. 178:186-191.
7. Cho, M.L., J.W. Kang, Y.M. Moon, H.J. Nam, J.Y. Jhun, S.B. Heo, H.T. Jin, S.Y. Min, J.H. Ju, K.S. Park, et al. 2006. STAT3 and NF-kappaB signal pathway is required for IL-23-mediated IL-17 production in spontaneous arthritis animal model IL-1 receptor antagonist-deficient mice. J. Immunol. 176:5652-5661.
8. Chung, Y., S.H. Chang, G.J. Martinez, X.O. Yang, R. Nurieva, H.S. Kang, L. Ma, S.S. Watowich, A.M. Jetten, Q. Tian, and C. Dong. 2009. Critical regulation of early Th17 cell differentiation by interleukin-1 signaling. Immunity. 30:576-587. http://dx.doi.org/10.1016/j.immuni.2009.02.007.
9. Cua, D.J., J. Sherlock, Y. Chen, C.A. Murphy, B. Joyce, B. Seymour, L. Lucian, W. To, S. Kwan, T. Churakova, et al. 2003. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature. 421:744-748. http://dx.doi.org/10.1038/nature01355.
10. Durant, L., W.T. Watford, H.L. Ramos, A. Laurence, G. Vahedi, L. Wei, H. Takahashi, H.W. Sun, Y. Kanno, F. Powrie, and J.J. O'Shea. 2010. Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis. Immunity. 32:605-615. http://dx.doi.org/10.1016/j.immuni.2010.05.003.
11. Gerondakis, S., R. Grumont, I. Rourke, and M. Grossmann. 1998. The regulation and roles of Rel/NF-kappa B transcription factors during lymphocyte activation. Curr. Opin. Immunol. 10:353-359. http://dx.doi.org/10.1016/S0952-7915(98)80175-1.
12. Gerondakis, S., R. Grumont, R. Gugasyan, L. Wong, I. Isomura, W. Ho, and A. Banerjee. 2006. Unravelling the complexities of the NFkappaB signalling pathway using mouse knockout and transgenic models. Oncogene. 25:6781-6799. http://dx.doi.org/10.1038/sj.onc.1209944.
13. Gonzalez, A., J.D. Katz, M.G. Mattei, H. Kikutani, C. Benoist, and D. Mathis. 1997. Genetic control of diabetes progression. Immunity. 7:873-883. http://dx.doi.org/10.1016/S1074-7613(00)80405-7.
14. He, Y.W., M.L. Deftos, E.W. Ojala, and M.J. Bevan. 1998. RORgamma t, a novel isoform of an orphan receptor, negatively regulates Fas ligand expression and IL-2 production in T cells. Immunity. 9:797-806. http://dx.doi.org/10.1016/S1074-7613(00)80645-7.
15. Hilliard, B.A., N. Mason, L. Xu, J. Sun, S.-E. Lamhamedi-Cherradi, H.-C. Liou, C. Hunter, and Y.H. Chen. 2002. Critical roles of c-Rel in autoimmune inflammation and helper T cell differentiation. J. Clin. Invest. 110:843-850.
16. Huguet, C., F. Bouali, P.J. Enrietto, D. Stehelin, B. Vandenbunder, and C. Abbadie. 1998. The avian transcription factor c-Rel is expressed in lymphocyte precursor cells and antigen-presenting cells during thymus development. Dev. Immunol. 5:247-261. http://dx.doi.org/10.1155/1998/58608.
17. + CD4 regulatory T cells. J. Exp. Med. 206:3001-3014. http://dx.doi.org/10.1084/jem.20091411.
18. Ivanov, I.I., B.S. McKenzie, L. Zhou, C.E. Tadokoro, A. Lepelley, J.J. Lafaille, D.J. Cua, and D.R. Littman. 2006. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 126:1121-1133. http://dx.doi.org/10.1016/j.cell.2006.07.035.
19. Köntgen, F., R.J. Grumont, A. Strasser, D. Metcalf, R. Li, D. Tarlinton, and S. Gerondakis. 1995. Mice lacking the c-rel proto-oncogene exhibit defects in lymphocyte proliferation, humoral immunity, and interleukin-2 expression. Genes Dev. 9:1965-1977. http://dx.doi.org/10.1101/gad.9.16.1965.
20. Lamhamedi-Cherradi, S.E., S. Zheng, B.A. Hilliard, L. Xu, J. Sun, S. Alsheadat, H.C. Liou, and Y.H. Chen. 2003. Transcriptional regulation of type I diabetes by NF-kappa B. J. Immunol. 171:4886-4892.
21. Langrish, C.L., Y. Chen, W.M. Blumenschein, J. Mattson, B. Basham, J.D. Sedgwick, T. McClanahan, R.A. Kastelein, and D.J. Cua. 2005. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J. Exp. Med. 201:233-240. http://dx.doi.org/10.1084/jem.20041257.
22. Laurence, A., C.M. Tato, T.S. Davidson, Y. Kanno, Z. Chen, Z. Yao, R.B. Blank, F. Meylan, R. Siegel, L. Hennighausen, et al. 2007. Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity. 26:371-381. http://dx.doi.org/10.1016/j.immuni.2007.02.009.
23. Liou, H.C., Z. Jin, J. Tumang, S. Andjelic, K.A. Smith, and M.L. Liou. 1999. c-Rel is crucial for lymphocyte proliferation but dispensable for T cell effector function. Int. Immunol. 11:361-371. http://dx.doi.org/10.1093/intimm/11.3.361.
24. Long, M., S.G. Park, I. Strickland, M.S. Hayden, and S. Ghosh. 2009. Nuclear factor-kappaB modulates regulatory T cell development by directly regulating expression of Foxp3 transcription factor. Immunity. 31:921-931. http://dx.doi.org/10.1016/j.immuni.2009.09.022.
25. Medvedev, A., A. Chistokhina, T. Hirose, and A.M. Jetten. 1997. Genomic structure and chromosomal mapping of the nuclear orphan receptor ROR gamma (RORC) gene. Genomics. 46:93-102. http://dx.doi.org/10.1006/geno.1997.4980.
26. Ouaaz, F., J. Arron, Y. Zheng, Y. Choi, and A.A. Beg. 2002. Dendritic cell development and survival require distinct NF-kappaB subunits. Immunity. 16:257-270. http://dx.doi.org/10.1016/S1074-7613(02)00272-8.
27. Pear, W.S., J.P. Miller, L. Xu, J.C. Pui, B. Soffer, R.C. Quackenbush, A.M. Pendergast, R. Bronson, J.C. Aster, M.L. Scott, and D. Baltimore. 1998. Efficient and rapid induction of a chronic myelogenous leukemia-like myeloproliferative disease in mice receiving P210 bcr/abl-transduced bone marrow. Blood. 92:3780-3792.
28. Pui, J.C., D. Allman, L. Xu, S. DeRocco, F.G. Karnell, S. Bakkour, J.Y. Lee, T. Kadesch, R.R. Hardy, J.C. Aster, and W.S. Pear. 1999. Notch1 expression in early lymphopoiesis influences B versus T lineage determination. Immunity. 11:299-308. http://dx.doi.org/10.1016/S1074-7613(00)80105-3.
29. Ruan, Q., V. Kameswaran, Y. Tone, L. Li, H.C. Liou, M.I. Greene, M. Tone, and Y.H. Chen. 2009. Development of Foxp3(+) regulatory t cells is driven by the c-Rel enhanceosome. Immunity. 31:932-940. http://dx.doi.org/10.1016/j.immuni.2009.10.006.
30. Shim, J.H., C. Xiao, A.E. Paschal, S.T. Bailey, P. Rao, M.S. Hayden, K.Y. Lee, C. Bussey, M. Steckel, N. Tanaka, et al. 2005. TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo. Genes Dev. 19:2668-2681. http://dx.doi.org/10.1101/gad.1360605.
31. Simek, S., and N.R. Rice. 1988. Detection and characterization of the protein encoded by the chicken c-rel protooncogene. Oncogene Res. 2:103-119.
32. Sun, H., S. Gong, R.J. Carmody, A. Hilliard, L. Li, J. Sun, L. Kong, L. Xu, B. Hilliard, S. Hu, et al. 2008. TIPE2, a negative regulator of innate and adaptive immunity that maintains immune homeostasis. Cell. 133:415-426. http://dx.doi.org/10.1016/j.cell.2008.03.026.
33. Sutton, C., C. Brereton, B. Keogh, K.H. Mills, and E.C. Lavelle. 2006. A crucial role for interleukin (IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis. J. Exp. Med. 203: 1685-1691. http://dx.doi.org/10.1084/jem.20060285.
34. Tumang, J.R., A. Owyang, S. Andjelic, Z. Jin, R.R. Hardy, M.L. Liou, and H.C. Liou. 1998. c-Rel is essential for B lymphocyte survival and cell cycle progression. Eur. J. Immunol. 28:4299-4312.
35. Veldhoen, M., and B. Stockinger. 2006. TGFbeta1, a "Jack of all trades": the link with pro-inflammatory IL-17-producing T cells. Trends Immunol. 27:358-361. http://dx.doi.org/10.1016/j.it.2006.06.001.
36. Villey, I., R. de Chasseval, and J.P. de Villartay. 1999. RORgammaT, a thymusspecific isoform of the orphan nuclear receptor RORgamma/TOR, is up-regulated by signaling through the pre-T cell receptor and binds to the TEA promoter. Eur. J. Immunol. 29:4072-4080.
37. Visekruna, A., M. Huber, A. Hellhund, E. Bothur, K. Reinhard, N. Bollig, N. Schmidt, T. Joeris, M. Lohoff, and U. Steinhoff. 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. http://dx.doi.org/10.1002/eji.200940260.
38. Wang, W., W.F. Tam, C.C. Hughes, S. Rath, and R. Sen. 1997. c-Rel is a target of pentoxifylline-mediated inhibition of T lymphocyte activation. Immunity. 6:165-174. http://dx.doi.org/10.1016/S1074-7613(00)80423-9.
39. Weaver, C.T., L.E. Harrington, P.R. Mangan, M. Gavrieli, and K.M. Murphy. 2006. Th17: an effector CD4 T cell lineage with regulatory T cell ties. Immunity. 24:677-688. http://dx.doi.org/10.1016/j.immuni.2006.06.002.
40. Xi, H., R. Schwartz, I. Engel, C. Murre, and G.J. Kersh. 2006. Interplay between RORgammat, Egr3, and E proteins controls proliferation in response to pre-TCR signals. Immunity. 24:813-826. http://dx.doi.org/10.1016/j.immuni.2006.03.023.
41. Yang, X.O., A.D. Panopoulos, R. Nurieva, S.H. Chang, D. Wang, S.S. Watowich, and C. Dong. 2007. STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J. Biol. Chem. 282:9358-9363. http://dx.doi.org/10.1074/jbc.C600321200.
42. Yang, X.O., B.P. Pappu, R. Nurieva, A. Akimzhanov, H.S. Kang, Y. Chung, L. Ma, B. Shah, A.D. Panopoulos, K.S. Schluns, et al. 2008. T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity. 28:29-39. http://dx.doi.org/10.1016/j.immuni.2007.11.016.
43. Zheng, Y., S. Josefowicz, A. Chaudhry, X.P. Peng, K. Forbush, and A.Y. Rudensky. 2010. Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature. 463:808-812. http://dx.doi.org/10.1038/nature08750.