Higher PGD(2) production by synovial mast cells from rheumatoid arthritis patients compared with osteoarthritis patients via miR-199a-3p/prostaglandin synthetase 2 axis

We previously reported that synovial mast cells (MCs) from patients with rheumatoid arthritis (RA) produced TNF-α in response to immune complexes via FcγRI and FcγRIIA. However, the specific functions of synovial MCs in RA remain unclear. This study aimed to elucidate those functions. Synovial tissues and fluid were obtained from RA and osteoarthritis (OA) patients undergoing joint replacement surgery. Synovium-derived, cultured MCs were generated by culturing dispersed synovial cells with stem cell factor. We performed microarray-based screening of mRNA and microRNA (miRNA), followed by quantitative RT-PCR-based verification. Synovial MCs from RA patients showed significantly higher prostaglandin systhetase (PTGS)1 and PTGS2 expression compared with OA patients’ MCs, and they produced significantly more prostaglandin D(2) (PGD(2)) following aggregation of FcγRI. PGD(2) induced IL-8 production by human group 2 innate lymphoid cells, suggesting that PGD(2)-producing MCs induce neutrophil recruitment into the synovium of RA patients. PTGS2 mRNA expression in RA patients’ MCs correlated inversely with miRNA-199a-3p expression, which down-regulated PTGS2. RA patients’ synovial fluid contained significantly more PGD(2) compared with OA patients’ fluid. Synovial MCs might regulate inflammation in RA through hyper-production of PGD(2) following FcRγ aggregation. Our findings indicate functional heterogeneity of human MCs among diseases.