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

Yanxia Guo | Zendy; Kenzie D. MacIsaac | Zendy; Yi Chen | Zendy; Richard Miller | Zendy; Renu Jain | Zendy; Barbara Joyce-Shaikh | Zendy; Heidi M. Ferguson | Zendy; IMing Wang | Zendy; Răzvan Cristescu | Zendy; John S. Mudgett | Zendy; Laura Engstrom | Zendy; Kyle J. Piers | Zendy; Gretchen A. Baltus | Zendy; Kenneth Barr | Zendy; Hongjun Zhang | Zendy; Huseyin Mehmet | Zendy; Laxminarayan G. Hegde | Zendy; Xiao Hu | Zendy; Laura Carter | Zendy; Thomas D. Aicher | Zendy; Gary D. Glick | Zendy; Dennis M. Zaller | Zendy; Abbas Hawwari | Zendy; Craig C. Correll | Zendy; Dallas C. Jones | Zendy; J. Daniel | Zendy

AI Assistant Blog Pricing

Home ZAIA Blog

Open Access

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

Author(s) -

Yanxia Guo,

Kenzie D. MacIsaac,

Yi Chen,

Richard Miller,

Renu Jain,

Barbara Joyce-Shaikh,

Heidi M. Ferguson,

IMing Wang,

Răzvan Cristescu,

John S. Mudgett,

Laura Engstrom,

Kyle J. Piers,

Gretchen A. Baltus,

Kenneth Barr,

Hongjun Zhang,

Huseyin Mehmet,

Laxminarayan G. Hegde,

Xiao Hu,

Laura Carter,

Thomas D. Aicher,

Gary D. Glick,

Dennis M. Zaller,

Abbas Hawwari,

Craig C. Correll,

Dallas C. Jones,

J. Daniel

Publication year - 2016

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2016.11.073

Subject(s) - rar related orphan receptor gamma , thymocyte , t cell receptor , biology , cd8 , transcription factor , t cell , experimental autoimmune encephalomyelitis , orphan receptor , cellular differentiation , microbiology and biotechnology , immune system , gene , immunology , genetics

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

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research