Essential role of a ThPOK autoregulatory loop in the maintenance of mature CD4⁺ T cell identity and function.

ABSTRACT: The transcription factor ThPOK (encoded by the Zbtb7b gene) controls homeostasis and differentiation of mature helper T cells, while opposing their differentiation to CD4⁺ intraepithelial lymphocytes (IELs) in the intestinal mucosa. Thus CD4 IEL differentiation requires ThPOK transcriptional repression via reactivation of the ThPOK transcriptional silencer element (Sil^ThPOK). In the present study, we describe a new autoregulatory loop whereby ThPOK binds to the Sil^ThPOK to maintain its own long-term expression in CD4 T cells. Disruption of this loop in vivo prevents persistent ThPOK expression, leads to genome-wide changes in chromatin accessibility and derepresses the colonic regulatory T (T_reg) cell gene expression signature. This promotes sele

SUBMITTER: Basu J 

PROVIDER: S-EPMC8887595 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature