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

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.
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Submitted on : Friday, January 21, 2022 - 12:01:05 PM
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Shawn Fahl, Alejandra Contreras, Anjali Verma, Xiang Qiu, Christelle Harly, et al.. The E protein-TCF1 axis controls γδ T cell development and effector fate. Cell Reports, Elsevier Inc, 2021, 34 (5), pp.108716. ⟨10.1016/j.celrep.2021.108716⟩. ⟨inserm-03538823⟩



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