Bcl11b prevents fatal autoimmunity by promoting T<sub>reg</sub> cell program and constraining innate lineages in T<sub>reg</sub> cells.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31457080.
- Also identified by DOI 10.1126/sciadv.aaw0480 and PMC identifier 6685710.
- Licence recorded as CC BY-NC.
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Abstract
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.
Medical subject headings
- Autoimmunity
- Fetus
- Repressor Proteins
- T-Lymphocytes, Regulatory
- Tumor Suppressor Proteins