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USP 4 interacts and positively regulates IRF 8 function via K48‐linked deubiquitination in regulatory T cells
Author(s) -
Lin Ruirong,
Nie Jia,
Ren Jiazi,
Liang Rui,
Li Dan,
Wang Ping,
Gao Chengjiang,
Zhuo Changhua,
Yang Chunkang,
Li Bin
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12668
Subject(s) - irf8 , ubiquitin , microbiology and biotechnology , downregulation and upregulation , regulatory t cell , il 2 receptor , chemistry , deubiquitinating enzyme , immune system , cytokine , immunology , biology , transcription factor , gene , t cell , biochemistry
CD 4 + CD 25 + regulatory T (Treg) cells comprise a unique subset of T cells required for maintaining immune homeostasis. However, the molecular mechanisms associated with the functional variety of Treg cells are not fully delineated. In the present study, we demonstrate that ubiquitin‐specific protease ( USP )4 physically interacted with interferon regulatory factor 8 ( IRF 8) function via a K48‐linked deubiquitinase, which stabilized IRF 8 protein levels in Treg cells. Depletion of USP 4 promoted the polyubiquitination of IRF 8 and the upregulation of type 2 inflammatory cytokine gene expression in Treg cells. Consistently, treatment of Treg cells with USP 4 inhibitor facilitated the polyubiquitination of IRF 8. In addition, the deficiency of USP 4 alleviated the suppressive function of Treg cells. Taken together, our results suggest that USP 4 interacts with and stabilizes IRF 8 to promote the suppressive function of Treg cells.