| First Author | Guo Y | Year | 2016 |
| Journal | Cell Rep | Volume | 17 |
| Issue | 12 | Pages | 3206-3218 |
| PubMed ID | 28009290 | Mgi Jnum | J:241891 |
| Mgi Id | MGI:5903823 | Doi | 10.1016/j.celrep.2016.11.073 |
| Citation | Guo Y, et al. (2016) Inhibition of RORgammaT Skews TCRalpha Gene Rearrangement and Limits T Cell Repertoire Diversity. Cell Rep 17(12):3206-3218 |
| abstractText | Recent studies have elucidated the molecular mechanism of RORgammaT transcriptional regulation of Th17 differentiation and function. RORgammaT was initially identified as a transcription factor required for thymopoiesis by maintaining survival of CD4+CD8+ (DP) thymocytes. While RORgamma antagonists are currently being developed to treat autoimmunity, it remains unclear how RORgammaT inhibition may impact thymocyte development. In this study, we show that in addition to regulating DP thymocytes survival, RORgammaT also controls genes that regulate thymocyte migration, proliferation, and T cell receptor (TCR)alpha selection. Strikingly, pharmacological inhibition of RORgamma skews TCRalpha gene rearrangement, limits T cell repertoire diversity, and inhibits development of autoimmune encephalomyelitis. Thus, targeting RORgammaT not only inhibits Th17 cell development and function but also fundamentally alters thymic-emigrant recognition of self and foreign antigens. The analysis of RORgamma inhibitors has allowed us to gain a broader perspective of the diverse function of RORgammaT and its impact on T cell biology. |
