The role of Drak2 in T cell expansion and survival (P1298)

Abstract

Drak2 is a serine-threonine kinase expressed most abundantly in T cells and B cells. We previously demonstrated that mice deficient in Drak2 (Drak2-/-) are resistant to disease in models of type 1 diabetes (T1D) and multiple sclerosis (MS) due to a defect in the accumulation of autoreactive T cells. Yet, Drak2-/- mice retain the ability to launch an effective immune response to pathogen infections. Current treatments for autoimmune diseases function by suppressing the immune system, which increases susceptibility to infections and tumors. Thus, Drak2 is a great potential therapeutic target to treat autoimmune disease, because its inhibition may alleviate autoimmune disease without compromising immunity to infections and tumors. Despite its potential as a target, it is unclear how Drak2 regulates the accumulation of autoreactive T cells. Our preliminary data show a decrease in the survival of Drak2-/- T cells compared to wildtype T cells following in vitro stimulation that is rescued by co-culture with wildtype T cells, suggesting a role for Drak2 in production of a critical survival factor. In addition, Drak2-/- T cells display defects in cell cycle progression, morphology, and actin polymerization following activation, implicating a role for Drak2 in the regulation of cytoskeletal dynamics. These data emphasize novel roles for Drak2 in T cell accumulation and suggest that, in the absence of Drak2, T cells exhibit defects in both survival and proliferation.