USP21 prevents the generation of T-helper-1-like Treg cells.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27857073.
- Also identified by DOI 10.1038/ncomms13559 and PMC identifier 5120220.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
FOXP3<sup>+</sup> Regulatory T (Treg) cells play a key role in the maintenance of immune homeostasis and tolerance. Disruption of Foxp3 expression results in the generation of instable Treg cells and acquisition of effector T-cell-like function. Here we report that the E3 deubiquitinase USP21 prevents the depletion of FOXP3 at the protein level and restricts the generation of T-helper-1-like Treg cells. Mice depleted of Usp21 specifically in Treg cells display immune disorders characterized by spontaneous T-cell activation and excessive T-helper type 1 (Th1) skewing of Treg cells into Th1-like Treg cells. USP21 stabilizes FOXP3 protein by mediating its deubiquitination and maintains the expression of Treg signature genes. Our results demonstrate how USP21 prevents FOXP3 protein depletion and controls Treg lineage stability in vivo.
Medical subject headings
- Forkhead Transcription Factors
- T-Lymphocytes, Regulatory
- Ubiquitin Thiolesterase