An antagonistic role for Fyn and Lyn kinases in autoimmune arthritis

Abstract

Abstract Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder characterized by infiltration of innate immune cells into the synovial joints, whose etiology is unclear. While the Fcγ receptor (FcγR) aggregation on innate inflammatory cells by auto-antibodies is a critical stimulus, much of FcγR signaling remains unknown. Previous research from our lab has shown that FcγR-mediated innate immune cell activation is antagonistically controlled by the Src family kinases, Fyn and Lyn. Our current study investigates the Fyn/Lyn dichotomy in controlling the severity of the inflammatory arthritis using K/BxN model or RA. Our preliminary studies show that Lyn deletion exacerbates joint swelling and clinical arthritis scores, while Fyn deletion reduces plasma inflammatory cytokine levels. These data indicate an antagonistic role for Fyn and Lyn kinases in autoimmune arthritis and support further study of the mechanisms by which these Src family kinases regulate inflammation.