Background: FOXP3 is a key transcription factor for the development and function of Tregs. Results: PIM1-mediated phosphorylation of FOXP3 at serine 422 decreased its DNA binding activity. Conclusion: PIM1 negatively regulates FOXP3-mediated transcriptional regulation and the suppressive activity of Tregs. Significance: PIM1 is a newly identified negative regulator of the immunosuppressive activity of Tregs.
RORγt is a key transcription factor that controls the development and function of inflammatory Th17. The mechanisms that regulate RORγt stability remain unclear. We report that Th17 cells highly express the deubiquitinase ubiquitin-specific protease (USP)4, which is essential for maintaining RORγt and Th17 cell function. Inhibition of the catalytic activity of USP4 with vialinin A, a compound derived from Chinese traditional medicine, dampened Th17 differentiation. USP4 interacted and deubiquitinated K48-linked polyubiquitination of RORγt, thereby promoting RORγt function and IL-17A transcription. Interestingly, TGF-β plus IL-6 enhanced USP4-mediated deubiquitination of RORγt. Moreover, USP4 and IL-17 mRNA, but not RORγt mRNA, were significantly elevated in CD4+ T cells from patients with rheumatic heart disease. Thus, USP4 could be a novel therapeutic target for the treatment of Th17-modulated autoimmune diseases.
Background: IFITM3 is a general antiviral host restriction factor against RNA viruses. Results: SET7-mediated monomethylation of IFITM3 at Lys-88 negatively affected its antiviral activity toward vesicular stomatitis virus (VSV) and influenza A virus (IAV) infection.
Conclusion:The monomethylation of antiviral host restriction factors may perturb their function. Significance: Targeting the SET7 pathway could provide new antiviral therapeutic strategies.
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