Journal
CELL REPORTS
Volume 34, Issue 5, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2021.108716
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Funding
- National Institutes of Health (NIH), United States [P01AI102853, P30CA006927]
- Commonwealth of Pennsylvania
- Bishop Fund
- Intramural Research Program of the National Institute on Aging, United States
- NIH [AI112579, AI121080, AI139874]
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This study reveals a regulatory axis where T cell receptor (TCR) signaling controls TCF1 expression, which in turn regulates gamma delta T lineage commitment and effector fate. The level of TCF1 expression plays a critical role in setting the threshold for gamma delta T lineage commitment and modulating effector fate.
TCF1 plays a critical role in T lineage commitment and the development of alpha beta lineage T cells, but its role in gamma delta 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 gamma delta T lineage commitment and effector fate. Indeed, the level of TCF1 expression plays an important role in setting the threshold for gamma delta T lineage commitment and modulates the ability of TCR signaling to influence effector fate adoption by gamma delta T lineage progenitors. This finding provides mechanistic insight into how TCR-mediated repression of E proteins promotes the development of gamma delta T cells and their adoption of the interleukin (IL)-17-producing effector fate. IL-17-producing gamma delta T cells have been implicated in cancer progression and in the pathogenesis of psoriasis and multiple sclerosis.
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