Histone lactylation promotes rheumatoid arthritis progression by increasing NFATc2 expression and the production of anti-lactylated histone autoantibodies.

ABSTRACT: Elevated lactate in the joint microenvironment of rheumatoid arthritis patients is crucial for disease progression, though the mechanism remains unclear. This study shows significantly increased global lactylation levels within fibroblast-like synoviocytes from RA patients compared to healthy controls, with lactylated proteins being enriched in histones. Furthermore, we find anti-lactylated histone autoantibodies present in RA patients that positively correlate with Disease Activity Score 28. Using CUT&Tag and RNA-seq, we identify NFATc2 as a key target gene regulated by histone H3 lysine 9 lactylation. Functional studies reveal that NFATc2 promotes migration of RA-FLSs. Additionally, using collagen antibody-induced arthritis and collagen-induced arthritis mouse models, we demonstrate that

SUBMITTER: Wu G 

PROVIDER: S-EPMC12514170 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature