TNF-α-driven m6A modification disrupts the immunoregulatory function of MSCs by regulating HDAC5-dependent super-enhancers.

ABSTRACT: Mesenchymal stem cells (MSCs) are extensively utilised to treat inflammatory diseases because of their strong immunosuppressive functions. However, these functions are strongly affected by the inflammatory microenvironment in vivo, which limits the therapeutic effect of MSCs. The present study demonstrated that TNF-α impairs the immunosuppressive effect of MSCs on T-cell proliferation. Mechanistically, TNF-α treatment decreased the expression of the H3 deacetylase HDAC5 and then led to increased super-enhancer (SE) signals and increased expression of leukaemia inhibitory factor (LIF), which results in the dysfunction of MSCs' immunosuppressive effect. Intravenous infusion of MSCs overexpressing HDAC5 increased therapeutic efficacy in SKG mice with inflammatory arthritis. Notably, TNF-α dow

SUBMITTER: Zhang W 

PROVIDER: S-EPMC12728190 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature