CXXC-finger protein 1 associates with FOXP3 to stabilize homeostasis and suppressive functions of regulatory T cells
FOXP3-expressing regulatory T (T reg ) 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 reg 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. Cxxc1 deletion in T reg 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 reg functional markers under steady-state conditions, which are essential for the maintenance of T reg cell homeostasis and their suppressive functions. Epigenetically, CXXC1 binds to the genomic regulatory regions of T reg program genes in mouse T reg cells, overlapping with FOXP3-binding sites. Given its critical role in T reg cell homeostasis, CXXC1 presents itself as a promising therapeutic target for autoimmune diseases.
Authors
- Qianying Xu (ORCID: https://orcid.org/0000-0001-8429-6993)
- Sijue Tao (ORCID: https://orcid.org/0000-0003-4377-1801)
- Kuai Liu (ORCID: https://orcid.org/0000-0003-3687-6402)
- Xianzhi Gao (ORCID: https://orcid.org/0000-0002-3934-982X)
- Yezhang Zhu (ORCID: https://orcid.org/0000-0001-6310-9108)
- Shuai Wang (ORCID: https://orcid.org/0000-0003-3533-8565)
- Yuxi Wang (ORCID: https://orcid.org/0000-0002-8402-3036)
- Jing Chen (ORCID: https://orcid.org/0009-0002-8156-8572)
- Xin Shen (ORCID: https://orcid.org/0009-0006-2699-3292)
- Yan Zeng
- Xiaoqian Liu (ORCID: https://orcid.org/0009-0006-1919-6519)
- Li Shen (ORCID: https://orcid.org/0000-0002-5696-2191)
- Lie Wang (ORCID: https://orcid.org/0000-0001-5094-012X)
- Chenxin Liu
- Xiaoyu Meng (ORCID: https://orcid.org/0000-0002-3190-9490)
- Linjia Dong
Institutions
- Tongji University (CN)
- University Medical Center (US)
- Cell Technology (China) (HK)
- Institute of Immunology (HR)
- Second Affiliated Hospital of Zhejiang University (CN)
- Tongji Hospital (CN)
- Hangzhou Medical College (CN)
- First Affiliated Hospital Zhejiang University (CN)
- Zhejiang University (CN)
Publication Details
- Journal
- eLife
- Published
- 2025-04-04
- DOI
- https://doi.org/10.7554/elife.103417.3
- Citations
- 1
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 0.80
Funders
- National Natural Science Foundation of China
- Zhejiang University
- Central Universities in China
- National Science and Technology Major Project
- Natural Science Foundation of Zhejiang Province