CD 49a promotes T ‐cell‐mediated hepatitis by driving T helper 1 cytokine and interleukin‐17 production

Summary It is becoming increasingly clear that the T ‐cell‐mediated immune response is important in many diseases. In this study, we used concanavalin A ( C on  A ) ‐induced hepatitis to investigate the role of CD 49a in the molecular and cellular mechanism of the T ‐cell‐mediated immune response. We found that CD 49a −/− mice had significantly reduced levels of serum alanine aminotransferase and were protected from C on  A ‐induced hepatitis. CD 49a deficiency led to decreased production of interferon‐ γ ( IFN ‐ γ ) and interleukin‐17A ( IL ‐17 A ) after C on  A injection. Furthermore, we found that hepatic CD4 + T cells and invariant natural killer T cells up‐regulated CD 49a expression, along with enhanced activation after C on  A injection, leading to production of inflammatory cytokines by these T cells. Blockade of CD 49a in vivo ameliorated C on  A ‐induced hepatitis with reduced production of IFN ‐ γ and IL ‐17 A . Hence, CD4 9a promoted C on  A ‐induced hepatitis through enhancing inflammatory cytokine production ( IFN ‐ γ and IL ‐17 A ) by CD 4 + T and invariant natural killer T cells. The protective effect of CD 49a blockade antibody suggested a new target therapeutic molecule for intervention of T ‐cell‐mediated liver injury.