SIRT3 inhibits fibroblast-like synoviocytes activation in rheumatoid arthritis through delactylation of H3K18
Authors' conclusion
SIRT3 suppresses RA progression by delactylating H3K18.
Study context
- Population
- RA patients' synovial tissue and peripheral blood mononuclear cells (PBMCs); CIA models; Fibroblast-like synoviocytes (FLS)
Methodological detailsH3K18la assessed by western blot and immunohistochemistry; CUT&Tag and RNA-sequencing; si-SIRT3 and SIRT3 agonist honokiol in FLS; macrophage-FLS co-culture
- H3K18la assessed by western blot and immunohistochemistry; CUT&Tag and RNA-sequencing; si-SIRT3 and SIRT3 agonist honokiol in FLS; macrophage-FLS co-culture
Main finding
As reported in the abstract
- Lactylation, particularly H3K18la, significantly elevated in RA synovial tissue
- Reducing H3K18la alleviated CIA model-associated symptoms and mitigated pathogenic effects of TNF-α on FLS; increasing H3K18la exacerbated TNF-α-induced pathology
- H3K18la and lactate co-regulated pathways included chemokine signalling and the inflammatory mediator of transient receptor potential channels
- SIRT3, a key regulator of H3K18la, downregulated in PBMCs from RA patients
- Reduced SIRT3 increased H3K18la in FLS and macrophages, which activated FLS
Original publication
SIRT3 inhibits fibroblast-like synoviocytes activation in rheumatoid arthritis through delactylation of H3K18. Rheumatology (Oxford). Published 17 September 2025. doi:10.
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