Inhibition of RORγT Skews TCRα Gene Rearrangement and Limits T Cell Repertoire Diversity

• DOI: 10.1016/j.celrep.2016.11.073
• Publication Date: 2016-12-22T07:00:19Z
• Authors: Yanxia Guo; Kenzie D. MacIsaac; Yi Chen; Richard J. Miller; Renu Jain; Barbara Joyce-Shaikh; Heidi Ferguson; I-Ming Wang; Razvan Cristescu; John Mudgett; Laura Engstrom; Kyle J. Piers; Gretchen A. Baltus; Kenneth Barr; Hongjun Zhang; Huseyin Mehmet; Laxminarayan G. H...; Xiao Hu; Laura L. Carter; Thomas D. Aicher; Gary Glick; Dennis Zaller; Abbas Hawwari; Craig C. Correll; Dallas C. Jones; Daniel J. Cua
• Keywords: Thymocyte; Orphan receptor

Recent studies have elucidated the molecular mechanism of RORγT transcriptional regulation Th17 differentiation and function. was initially identified as a transcription factor required for thymopoiesis by maintaining survival CD4+CD8+ (DP) thymocytes. While RORγ antagonists are currently being developed to treat autoimmunity, it remains unclear how inhibition may impact thymocyte development. In this study, we show that in addition regulating DP thymocytes survival, also controls genes regulate migration, proliferation, T cell receptor (TCR)α selection. Strikingly, pharmacological skews TCRα gene rearrangement, limits repertoire diversity, inhibits development autoimmune encephalomyelitis. Thus, targeting not only function but fundamentally alters thymic-emigrant recognition self foreign antigens. The analysis inhibitors has allowed us gain broader perspective diverse its on biology.