Regulation of endogenous dsRNA by GSK3b in CD8 cells 4129

Abstract Description Glycogen Synthase Kinase 3b (GSK3b) is a constitutively active kinase that is ubiquitously expressed and promotes cell death. Inactivation of GSK3b is tonically required to support cell survival. The canonical mechanism for GSK3b inactivation to sustain cell survival is by phosphorylation on Ser9 by AKT, but the non-canonical inactivation of GSK3b by phosphorylation on Ser389 by p38 MAPK is required for DNA repair of DNA double strand breaks (DSB). Our recent studies have revealed a new function of GSK3b in effector CD8 cells. We will show that failure to inactivate GSK3b through Ser389 phosphorylation results in increased levels of endogenous dsRNA generated in mitochondria in effector CD8 cells. Sustained activation of GSK3b does not affect survival or expansion of effector CD8 cells. Importantly, the increased levels of endogenous dsRNA trigger the production of type I IFN by effector CD8 cells during expansion in the absence of TCR stimuli. This is the first description of effector CD8 cells being able to produce type I IFN. These results can have a major impact in the area of T cell therapy for cancer.. Funding Sources NIH R21AI167201 Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)