CXXC-finger protein 1 associates with FOXP3 to stabilize homeostasis and suppressive functions of regulatory T cells

Xiaoyu Meng; Yezhang Zhu; Kuai Liu; Yuxi Wang; Xiaoqian Liu; Chenxin Liu; Yan Jun Zeng; Shuai Wang; Xianzhi Gao; Xin Shen; Jing Chen; Sijue Tao; Qianying Xu; Linjia Dong; Li Shen; Lie Wang

doi:10.7554/elife.103417.3

ImmunologybioRxivSep 30, 2024

CXXC-finger protein 1 associates with FOXP3 to stabilize homeostasis and suppressive functions of regulatory T cells

Xiaoyu Meng iD, Yezhang Zhu iD, Kuai Liu iD, Yuxi Wang iD, Xiaoqian Liu iD, Chenxin Liu iD, Yan Jun Zeng iD, Shuai Wang iD, Xianzhi Gao iD, Xin Shen iD, Jing Chen iD, Sijue Tao iD, Qianying Xu iD, Linjia Dong, Li Shen iD, Lie Wang iD

PDF DOI Preprint

Post to X

Threads on X Post to Bluesky Threads on Bluesky

Abstract

FOXP3-expressing regulatory T (Treg) 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 Treg 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 Treg 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 Treg functional markers under steady-state conditions, which are essential for the maintenance of Treg cell homeostasis and their suppressive functions. Epigenetically, CXXC1 binds to the genomic regulatory regions of Treg program genes in mouse Treg cells, overlapping with FOXP3 binding sites. Given its critical role in Treg cell homeostasis, CXXC1 presents itself as a promising therapeutic target for autoimmune diseases.