The role of CdK5 in the activation and effector function of T cells in experimental autoimmune uveitis (BA14P.216)

Abstract

Abstract The activation and survival of T cells are both essential for the development and progression of uveitis. Cyclin-dependent kinas 5 (Cdk5) is a unique member of Cdk family that forms a complex with p35 (CDK5R1) and modulates the function of many proteins through proline-directed serine threonine phosphorylation. Our previous study showed that Cdk5 expression and activity is induced during T cell activation, but it is unclear whether CdK5 is implicated in experimental autoimmune uveitis (EAU). In this study, we found that CD4+CD44+ T cells have a higher level of Cdk5 expression. Inhibition of CdK5 by a small molecule inhibitor (roscovitine) led to the decrease in the number of activated CD4+CD44+ T lymphocytes, which coincided with increased T cell apoptosis. We observed increased expression and activity of CdK5, p35 (and its cleaved product p25) in the eyes and lymphocytes of C57BL/6 mice induced to develop EAU by immunization with interphotoreceptor retinoid-binding protein peptide 1-20 (IRBP1-20). In addition, roscovitine significantly suppressed proliferation of and cytokine production in T cells from mice with the disease in vitro. These results demonstrate that CdK5 plays a critical role in T cell activation during the pathogenesis of uveitis and suggests that targeting CdK5 may be a novel therapeutic strategy for treating T cell-mediated uveitis.