The E protein-TCF1 axis controls ?? T cell development and effector fate.

ABSTRACT: TCF1 plays a critical role in T lineage commitment and the development of ?? lineage T cells, but its role in ?? T cell development remains poorly understood. Here, we reveal a regulatory axis where T cell receptor (TCR) signaling controls TCF1 expression through an E-protein-bound regulatory element in the Tcf7 locus, and this axis regulates both ?? T lineage commitment and effector fate. Indeed, the level of TCF1 expression plays an important role in setting the threshold for ?? T lineage commitment and modulates the ability of TCR signaling to influence effector fate adoption by ?? T lineage progenitors. This finding provides mechanistic insight into how TCR-mediated repression of E proteins promotes the development of ?? T cells and their adoption of the interleukin (IL)-17-producing effector fate. IL-17-producing ?? T cells have been implicated in cancer progression and in the pathogenesis of psoriasis and multiple sclerosis.

SUBMITTER: Fahl SP 

PROVIDER: S-EPMC7919611 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature