USP 4 interacts and positively regulates IRF 8 function via K48‐linked deubiquitination in regulatory T cells

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.