The importance of PI3Kgamma signaling in the activation of immune CD8 T cells in hypertension
Hypertension (HTN) is now defined as an immune disorder. CD8 effector T cells are the major players in the infiltration of target organs in hypertension, moreover it is still unknown the intracellular signaling mediating the differentiation from naïve T cells to effector T cells. Phosphatidylinositol-3-kinase gamma (PI3Kg), a lipid kinase mainly expressed in immune and cardiovascular systems, is a typical signaling downstream of G protein coupled receptors that regulate cell trafficking and migration of effector CD8 T cells. In the past, my laboratory have described a crucial role of PI3Kg in hypertension. Here we will test the hypothesis that this signaling could be a critical regulator of immune cells trafficking in hypertension and we will deepen the contribution of these cells in altering mechanisms relevant to blood pressure (BP) regulation.
By taking advantage of a knock in mouse model, expressing a constitutively active PI3Kg isoform (PI3Kg CX/CX), we will realize the experimental settings allowing to assess the role of PI3Kg in the crosstalk between immune cells and hypertension.
We suppose that PI3Kg signaling in CD8 T cells is crucial for their accumulation in target organs of hypertension, likely contributing to blood pressure increase.