Histone lactylation in fibroblast-like synoviocytes drives CXCL1-mediated immune cells recruitment in autoimmune arthritis

In this study, elevated plasma lactate levels were identified as a robust clinical diagnostic biomarker for autoimmune arthritis based on the analysis of a publicly available metabolomics dataset. Further investigations demonstrated that lactate-mediated histone lactylation is notably elevated in synovial FLS derived from autoimmune arthritis patients. This epigenetic modification was associated with increased expression of the chemokine CXCL1, which promotes immune cell recruitment.

Therapeutic interventions targeting this pathway—either through CXCL1 neutralization or inhibition of histone lactylation—effectively reduced immune cell infiltration, alleviated joint inflammation, and mitigated bone destruction in CIA and SKG mouse models of autoimmune arthritis. These findings underscore the pivotal role of histone lactylation in mediating the recruitment phenotype of FLS and highlight its potential as a novel therapeutic target for autoimmune arthritis.