Publication Date:
2019
Description:
〈p〉Regulatory T (T〈sub〉reg〈/sub〉) cells are essential for peripheral tolerance and rely on the transcription factor (TF) Foxp3 for their generation and function. Several other TFs are critical for the T〈sub〉reg〈/sub〉 cell program. We found that mice deficient in Bcl11b TF solely in T〈sub〉reg〈/sub〉 cells developed fatal autoimmunity, and Bcl11b-deficient T〈sub〉reg〈/sub〉 cells had severely altered function. Bcl11b KO T〈sub〉reg〈/sub〉 cells showed decreased functional marker levels in homeostatic conditions, inflammation, and tumors. Bcl11b controlled expression of essential T〈sub〉reg〈/sub〉 program genes at steady state and in inflammation. Bcl11b bound to genomic regulatory regions of T〈sub〉reg〈/sub〉 program genes in both human and mouse T〈sub〉reg〈/sub〉 cells, overlapping with Foxp3 binding; these genes showed altered chromatin accessibility in the absence of Bcl11b. Additionally, Bcl11b restrained myeloid and NK cell programs in T〈sub〉reg〈/sub〉 cells. Our study provides new mechanistic insights on the T〈sub〉reg〈/sub〉 cell program and identity control, with major implications for therapies in autoimmunity and cancer.〈/p〉
Electronic ISSN:
2375-2548
Topics:
Natural Sciences in General