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

Cell Rep. 2021 Feb 2;34(5):108716. doi: 10.1016/j.celrep.2021.108716.

Abstract

TCF1 plays a critical role in T lineage commitment and the development of αβ lineage T cells, but its role in γδ 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 γδ T lineage commitment and effector fate. Indeed, the level of TCF1 expression plays an important role in setting the threshold for γδ T lineage commitment and modulates the ability of TCR signaling to influence effector fate adoption by γδ T lineage progenitors. This finding provides mechanistic insight into how TCR-mediated repression of E proteins promotes the development of γδ T cells and their adoption of the interleukin (IL)-17-producing effector fate. IL-17-producing γδ T cells have been implicated in cancer progression and in the pathogenesis of psoriasis and multiple sclerosis.

Keywords: E proteins; T cell receptor (TCR); TCF1; TCR signaling; development; interleukin-17; γδ T cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Hepatocyte Nuclear Factor 1-alpha / metabolism*
  • Humans
  • Mice
  • Models, Immunological
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • Signal Transduction

Substances

  • Hepatocyte Nuclear Factor 1-alpha
  • Hnf1a protein, mouse
  • Receptors, Antigen, T-Cell, gamma-delta