Arginine methylation of FOXP3 is crucial for the suppressive function of regulatory T cells
Arginine methylation of FOXP3 is crucial for the suppressive function of regulatory T cells
复制标题
FOXP3的精氨酸甲基化对调节性T细胞的抑制功能至关重要
DOI：
10.1016/j.jaut.2018.09.011
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发表时间：
2019-02-01
影响因子：
12.8
通讯作者：
Hirano, Naoto
中科院分区：
文献类型：
--
作者：
Kagoya, Yuki;Saijo, Hiroshi;Hirano, Naoto
Forkhead box transcription factor 3 (FOXP3) plays a pivotal role in the suppressive function of regulatory T cells. In addition to mRNA levels, FOXP3 activity can also be controlled by posttranslational mechanisms, which have not been studied in a comprehensive manner. Through extensive screening using selective inhibitors, we demonstrate that the inhibition of type I protein arginine methytransferases (PRMTs) attenuates the suppressive functions of regulatory T cells. FOXP3 undergoes methylation on arginine residues at positions 48 and 51 by interacting with protein arginine methyltransferase 1 (PRMT1). The inhibition of arginine methylation confers gene expression profiles representing type I helper T cells to FOXP3(+) T cells, which results in attenuated suppressive activity. A methylation-defective mutant of FOXP3 displays less potent activity to suppress xenogeneic graft-versus-host disease in vivo. These results elucidate an important role of arginine methylation to enhance FOXP3 functions and are potentially applicable to modulate regulatory T cell functions.
