The E protein-TCF1 axis controls γδ T cell development and effector fate - Archive ouverte HAL Access content directly
Journal Articles Cell Reports Year : 2021

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

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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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Dates and versions

inserm-03538823 , version 1 (21-01-2022)

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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, 2021, 34 (5), pp.108716. ⟨10.1016/j.celrep.2021.108716⟩. ⟨inserm-03538823⟩
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