BMSC-derived exosomes improve rheumatoid arthritis by regulating Th17 cell differentiation through targeting PRDM1.

BACKGROUND: Rheumatoid arthritis (RA) is categorized as an autoimmune condition. Bone marrow-derived mesenchymal stromal cell (BMSC) derived exosome (BMSC-Exo) exert vital character in RA. We aimed to investigate the regulatory mechanism of BMSC-Exo in alleviating RA. METHODS: BMSC was isolated from mouse bone marrow. Collagen-induced arthritis (CIA) was induced by injecting bovine type II collagen and complete Freund's adjuvant. Arthritis score, incidence, and withdrawal threshold were assessed. Hematoxylin-eosin staining was used to observe knee joint damage. CD4(+) T cells were isolated from the spleen, and T helper 17 (Th17) proportions were measured by flow cytometry. Caspase-1 activity was assessed. RESULTS: BMSC-Exo injection reduced arthritis score and incidence of arthritis, and elevated the withdrawal threshold of CIA mice. BMSC-Exo also alleviated knee damage in CIA mice and reduced the Th17 proportion. BMSC-Exo down-regulated inflammatory cytokine levels, as well as caspase-1 activity. BMSC-Exo up-regulated PR Domain Zinc Finger Protein 1 (PRDM1) levels. PRDM1 knockdown in BMSC down-regulated PRDM1 expression in Exo but did not affect up-regulated PRDM1 expression in CD4(+) T cells. In vivo, BMSC-Exo affected RA pathology by acting on PRDM1. CONCLUSIONS: BMSC-Exo improved RA by promoting PRDM1 expression in CD4(+) T cells and inhibiting Th17 cell differentiation.