CCR10 promotes blood pressure elevations and renal damage in a mouse model of hypertension

Abstract

Abstract Hypertension is the leading cause of morbidity and mortality worldwide. Emerging evidence suggests that pro-inflammatory immune cells play a central role in hypertension and its associated end-organ damage. Regulatory T cells (Tregs) are immunosuppressive, however their role in hypertension remains unclear. Interestingly, Tregs can be pathogenic in some disease states by limiting angiogenesis. We recently identified a selective decrease in circulating CCR10 +Tregs in hypertensive humans. CCR10 is a chemokine receptor important for recruitment of immune cells, particularly Tregs, to the skin. Prior studies have demonstrated skin microvascular rarefaction in hypertension as a mechanism to raise blood pressure (BP). We hypothesized that CCR10 +Tregs promote hypertension through skin infiltration leading to enhanced microvascular rarefaction. We demonstrate that mice with angiotensin II (Ang II) infusion to induce hypertension have an increased abundance of CCR10 +Tregs in the skin compared to normotensive controls. In addition, mice with CCR10 deficiency exhibit increased CD31 +endothelial cells in the skin after Ang II infusion compared to wild type controls, consistent with reduced cutaneous microvascular rarefaction. Moreover, CCR10-deficient mice have lower Ang II-induced increases in systolic BP and lower levels of albuminuria. Finally, using PrediXcan, we demonstrate that higher genetically predicted levels of CCR10 are associated with increased risk 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 recruitment to the skin leading to microvascular rarefaction.