Effects of dioscin from Dioscorea nipponica on TL1A/DR3 and Th9 cells in a collagen-induced arthritis mouse model.

Rheumatoid arthritis (RA) is a systemic autoimmune disease, and TL1A and its receptor DR3 play important roles in its pathogenesis. Th9 cells are involved in RA development. Dioscin from Dioscorea nipponica (DDN) has a therapeutic effect on RA, but its effect on TL1A/DR3 and Th9 cells remains unclear. A collagen-induced arthritis (CIA) model was established in DBA/1 mice, and the therapeutic effects of DDN were determined using pathological sections and arthritis index scores. Western blotting and PCR were used to detect TL1A, DR3, PU.1, TGF-β and IRF-4. Enzyme-linked immunosorbent assay was used to detect the expression of TL1A and IL-9 in the serum. Immunofluorescence was used to detect the localization and expression of TL1A, DR3, and PU.1 in synovial tissue. Flow cytometry was used to detect TL1A and DR3 expression in different immune cells and Th9 cells. DDN ameliorated bone destruction, inflammatory cell infiltration, synovial inflammation, cartilage tissue destruction, and proteoglycan loss. DDN downregulated TL1A, DR3, and PU.1 in the synovium of the lymph nodes and spleen and TL1A and IL-9 in the serum. DDN decreased the number of TL1A-expressing APCs and macrophages, DR3-expressing CD4 + T cells, and Th9 cells. Th9 cell differentiation-related factors TGF-β and IRF-4 were also inhibited by DDN. We conclude that DNN inhibited the expression of TL1A/DR3 in CIA mice and suppressed the expression of the Th9 cell-specific transcription factor PU.1, Th9 cell number, and IL-9 secretion. DDN inhibited the function of Th9 cells by targeting TGF-β and IRF-4 in the TL1A/DR3 pathway, thereby reducing inflammation.