Meningeal IL-17 producing T cells mediate cognitive impairment in salt-sensitive hypertension

Abstract

ABSTRACTHypertension, a disease afflicting over one billion individuals worldwide, is a leading cause of cognitive impairment, the mechanisms of which remain poorly understood. In a mouse model of hypertension involving brain angiotensin signaling, we found that the neurovascular and cognitive dysfunction depends on IL-17, a cytokine elevated in the circulation of hypertensive individuals. However, neither circulating IL-17 or brain angiotensin signaling could account in full for the dysfunction. Rather, IL-17 produced by meningeal T-cells was the major culprit by activating IL-17 receptors on brain associated macrophages. Accordingly, depleting brain macrophages or suppressing meningeal T cells completely rescued cognitive function without attenuating blood pressure elevation, circulating IL-17 or brain angiotensin signaling. The data unveil a critical role of meningeal T-cells and macrophage IL-17 signaling in the neurovascular and cognitive dysfunction of hypertension and suggest novel therapies to counteract the devastating effects of hypertension on cognitive health.