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Fahl SP , Contreras AV , Verma A , Qiu X , Harly C , Radtke F , Zúñiga-Pflücker JC , Murre C , Xue HH , Sen JM , Wiest DL
The E protein-TCF1 axis controls γδ T cell development and effector fate
Cell Rep. 2021 Feb 2;34(5) :108716
PMID: 33535043    PMCID: PMC7919611    URL: https://www.ncbi.nlm.nih.gov/pubmed/33535043
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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.
2211-1247 Fahl, Shawn P Contreras, Alejandra V Verma, Anjali Qiu, Xiang Harly, Christelle Radtke, Freddy Zúñiga-Pflücker, Juan Carlos Murre, Cornelis Xue, Hai-Hui Sen, Jyoti Misra Wiest, David L Journal Article United States Cell Rep. 2021 Feb 2;34(5):108716. doi: 10.1016/j.celrep.2021.108716.