Acidosis regulates immune progression in rheumatoid arthritis by promoting the expression of cytokines and co-stimulatory molecules in synovial fibroblasts

Bulk RNA-seq and RNA-seq identified 56 differentially expressed cytokines at their intersection. Functional enrichment analysis demonstrated that acid stimulation enhanced cytokine secretion and T cell chemotaxis in RA synovial fibroblasts (RASFs). Cytokine array revealed that acid exposure increased the accumulation of growth factors (e.g., FGF, VEGF) by over twofold and promoted the expression of multiple inflammatory and chemotactic factors. Immune state analysis indicated that acid stimulation induced a complex immune landscape by upregulating co-stimulatory and antigen-presenting molecules. Proteomics showed that acid stress enhanced mitochondrial function and triggered metabolic reprogramming in RASFs. Integrated transcriptomic and proteomic analyses revealed that AP1 regulates gene expression in RASFs, with its activation further confirmed by Western blotting and immunofluorescence.