Abstract P186: CCR10 Promotes Blood Pressure Elevations And Renal Damage In A Mouse Model Of Hypertension

Emerging evidence suggests inflammation plays a key role in hypertension and its associatedend-organ damage. Regulatory T cells (Tregs) function primarily by limiting inflammation andare considered protective in the pathogenesis of hypertension. However, Tregs also havetissue-specific functions and have been found to play pathogenic roles in some chronicdiseases by limiting angiogenesis. As such, the role of Tregs and its subsets in chronichypertension remains unclear. Recently, we identified CCR10 + Tregs as an immune populationselectively decreased in the circulation of hypertensive patients. CCR10 is a chemokinereceptor important for recruitment of immune cells to the skin. Although skin has not been wellstudied in hypertension, prior reports in humans demonstrate that loss of skin microvessels(microvascular rarefaction) occurs as a putative mechanism by which blood pressure (BP) isincreased. Thus, we hypothesized that CCR10 + Tregs promote hypertension through skininfiltration leading to enhanced microvascular rarefaction. Herein, we demonstrate that,compared to normotensive controls, mice with Angiotensin II (Ang II)-induced hypertension haveincreased abundance of CCR10 + Tregs in the skin (p=0.0004) with a corresponding decrease incirculation (p=0.003). These mice also displayed increased cutaneous levels of CCL27(p=0.0007), a ligand for CCR10. Among circulating lymphocytes in normotensive mice, wefound that Tregs express the highest frequency of CCR10 (p=0.0007). Importantly, wedemonstrate that CCR10-deficient mice (CCR10 -/- ) are more resistant to Ang II-induced systolicblood pressure elevations (p=0.004) and albuminuria (p=0.01) compared to wild type mice.CCR10 -/- mice also exhibit higher levels of cutaneous arteriolar density (p=0.02) and VEGFA(p=0.009), consistent with reduced skin microvascular rarefaction. Finally, using PrediXcan, wedemonstrate that higher genetically predicted levels of CCR10 are associated with increasedrisk of hypertension in humans. Taken together, our data suggest that CCR10 promotes Ang II-induced BP elevations and renal damage in mice, at least in part by promoting Treg recruitmentto the skin leading to microvascular rarefaction.