CXXC-finger protein 1 associates with FOXP3 to stabilize homeostasis and suppressive functions of regulatory T cells.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40183773.
- Also identified by DOI 10.7554/eLife.103417 and PMC identifier 11970909.
- 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-expressing regulatory T (T<sub>reg</sub>) cells play a pivotal role in maintaining immune homeostasis and tolerance, with their activation being crucial for preventing various inflammatory responses. However, the mechanisms governing the epigenetic program in T<sub>reg</sub> cells during their dynamic activation remain unclear. In this study, we demonstrate that CXXC-finger protein 1 (CXXC1) interacts with the transcription factor FOXP3 and facilitates the regulation of target genes by modulating H3K4me3 deposition. <i>Cxxc1</i> deletion in T<sub>reg</sub> cells leads to severe inflammatory disease and spontaneous T cell activation, with impaired immunosuppressive function. As a transcriptional regulator, CXXC1 promotes the expression of key T<sub>reg</sub> functional markers under steady-state conditions, which are essential for the maintenance of T<sub>reg</sub> cell homeostasis and their suppressive functions. Epigenetically, CXXC1 binds to the genomic regulatory regions of T<sub>reg</sub> program genes in mouse T<sub>reg</sub> cells, overlapping with FOXP3-binding sites. Given its critical role in T<sub>reg</sub> cell homeostasis, CXXC1 presents itself as a promising therapeutic target for autoimmune diseases.
Medical subject headings
- T-Lymphocytes, Regulatory
- Forkhead Transcription Factors
- Homeostasis