Citations 1
Inflammation negatively regulates FOXP3 and regulatory T-cell function via DBC1
Gao, Yayi , Tang, Jiayou , Li, Qiang , Nie, Jia , Lin, Fang , Wu, Qingsi, Chen, Zuojia , Gao, Zhimei, Fan, Huimin , Tsun, Andy , Shen, Jijia, Chen, Guihua , Liu, Zhongmin , Olsen, Nancy J. , Zheng, Song Guo , Li, Bin , Chen, Weiqian , Lou, Zhenkun
Proceedings of the National Academy of Sciences | June 10, 2015 | Volume: 112 | Issue: 25 | Pages: No page available
Significance Treg cells suppress excessive and aberrant immune responses. Impaired function or homeostasis of Treg cells would induce severe autoimmune and inflammatory diseases. Forkhead box P3 (FOXP3), as a master regulator of Treg cells, forms a large complex with other binding factors to modulate Treg-cell function subtly in pathological and physiological conditions. We identified that Deleted in breast cancer 1 (DBC1) is an essential subunit of the FOXP3 complex in human CD4 + Treg cells. Our results show that the inflammatory cytokines TNF-α or IL-6 trigger FOXP3 degradation, whereas downregulation of DBC1 expression prevents FOXP3 degradation and maintains Treg-cell function under inflammatory stimuli in vitro and in vivo. These findings unveil a previously unidentified pathway for therapeutically modulating FOXP3 + Treg-cell stability under inflammation.