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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. Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.


Shawn P Fahl, Alejandra V Contreras, Anjali Verma, Xiang Qiu, Christelle Harly, Freddy Radtke, Juan Carlos Zúñiga-Pflücker, Cornelis Murre, Hai-Hui Xue, Jyoti Misra Sen, David L Wiest. The E protein-TCF1 axis controls γδ T cell development and effector fate. Cell reports. 2021 Feb 02;34(5):108716

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PMID: 33535043

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