The roles of cytokines in the development of autoimmune deseases

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Rheumatoid arthritis (RA) is one of the most serious medical problems worldwide with approximately 1% of the people in the world affected. The disease is autoimmune in nature and characterized by chronic inflammation of the synovial tissues in multiple joints. High levels of inflammatory cytokine expression in the joints are characteristics of the disease, although the pathogenesis has not been elucidated completely. We have been studying the pathogenesis of the disease using two arthritis models that we originally developed ; HTLV-I transgenic (HTLV-I Tg) mice and IL-1 receptor antagonist-deficient (IL-1Ra KO) mice. In this study, we analyzed the roles of IL-17 family cytokines in the development of autoimmune diseases and the mechanisms of Th17 induction through DC activation. We found that 1) IL-17A, but not IL-17F, plays an important role in the development of autoimmune diseases and inflammatory diseases, 2) Both IL-17A and IL-17F play important roles in the host defense against bacterial infections, 3) Both Dectin-1 and Dectin-2, which is a receptor for β-glucans and α-mannans, respectively, on DCs, induce Th17 differentiation through activation of DCs, and play important role in the host defense against fungal infections. These findings should be of use for the development of new therapeutics against autoimmune diseases and fungal infection.