SENP3 maintains the stability and function of regulatory T cells via BACH2 deSUMOylation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30089837.
- Also identified by DOI 10.1038/s41467-018-05676-6 and PMC identifier 6082899.
- 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
Regulatory T (Treg) cells are essential for maintaining immune homeostasis and tolerance, but the mechanisms regulating the stability and function of Treg cells have not been fully elucidated. Here we show SUMO-specific protease 3 (SENP3) is a pivotal regulator of Treg cells that functions by controlling the SUMOylation and nuclear localization of BACH2. Treg cell-specific deletion of Senp3 results in T cell activation, autoimmune symptoms and enhanced antitumor T cell responses. SENP3-mediated BACH2 deSUMOylation prevents the nuclear export of BACH2, thereby repressing the genes associated with CD4<sup>+</sup> T effector cell differentiation and stabilizing Treg cell-specific gene signatures. Notably, SENP3 accumulation triggered by reactive oxygen species (ROS) is involved in Treg cell-mediated tumor immunosuppression. Our results not only establish the role of SENP3 in the maintenance of Treg cell stability and function via BACH2 deSUMOylation but also clarify the function of SENP3 in the regulation of ROS-induced immune tolerance.
Medical subject headings
- Basic-Leucine Zipper Transcription Factors
- Immune Tolerance
- Peptide Hydrolases
- Sumoylation
- T-Lymphocytes, Regulatory