PI3Kγ signaling controls trafficking of CD8T cells between lymphoid and non-lymphoid organs and drives hypertension in a murine model.

Abstract

Activated immune cells infiltrate the vasculature during the pathophysiology of hypertension by establishing a vascular-immune interface that contributes to blood pressure dysregulation and organ failure. Many observations indicate a key role of CD8T cells in hypertension but mechanisms regulating their activation and interplay with the cardiovascular system are still unknown. In murine model, here we show that a specific member of the phosphoinositide-3-kinases (PI3K) family of lipid kinases, PI3Kγ, is a key intracellular signaling of CD8T cells activation and RANTES/CCL5 secretion in hypertension: CCL5-CCR5 signaling is crucial for the establishment of the vascular-immune interface in peripheral organs, lastly contributing to CD8tissue infiltration, organ dysfunction and blood pressure elevation. Our studies identify PI3Kγ as a booster of effector CD8T cell function, even in the absence of external stimuli. Lastly, an enhanced PI3Kγ signaling mediates the bystander activation of CD8T cells and proves effective in transferring the hypertensive phenotype between mice.