Baricitinib alleviates interstitial lung disease in CIA mice by inhibiting macrophage polarization and increase exosomal miR-126a-3p with anti-fibrotic activity in vitro

Background: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a severe condition with an unclear pathogenesis. Here, we investigated the effects of baricitinib on lung fibrosis progression. Methods: using Western blotting and immunofluorescence staining. The cytokine levels in supernatants were measured using ELISA, and macrophage-derived exosomes were identified using transmission electron microscopy and Western blotting, followed by microRNA sequencing analyses. miR-126a-3p-regulated genes were identified using dual-luciferase reporter assays. Results: , baricitinib downregulated the expression of arginase-1, CD206 and MerTK in macrophages and TGF-β and IL-10 in supernatants. Baricitinib also increased miR-126a-3p expression in macrophage-derived exosomes. miR-126a-3p exerted antifibrotic effects by regulating apoptosis and autophagy via the PI3K/AKT1/mTOR pathway. Silencing JAK1 reduced JAK1 and JAK2 expression. Conclusion: using NIH3T3 cell.