Dysregulation of T cell subsets in the pathogenesis of hypertension

Abstract

Essential hypertension (EH) and its complications have had a severe impact on public health. However, the underlying mechanisms of the pathogenesis of EH remain largely unknown. Recent investigations, predominantly in rats and mice, have provided evidence that dysregulation of distinct functions of T lymphocyte subsets is a potentially important mechanism in the pathogenesis of hypertension. We critically reviewed recent findings and propose an alternative explanation on the understanding of dysfunctional T lymphocyte subsets in the pathogenesis of hypertension. The hypothesis is that hypertensive stimuli, directly and indirectly, increase local IL-6 levels in the cardiovascular system and kidney, which may promote peripheral imbalance in the differentiation and ratio of Th17 and T regulatory cells. This results in increased IL-17 and decreased IL-10 in perivascular adipose tissue and adventitia contributing to the development of hypertension in experimental animal models. Further investigation in the field is warranted to inform new translational advances that will promote to understand the pathogenesis of EH and develop novel approaches to prevent and treat EH.

Fig. 1

A schematic diagram shows that hypertensive stimuli through interaction of genetic (e.g., dysfunction of autonomous nervous system in SHR) and environmental factors (e.g., obesity, high-salt diet, and vitamin D deficiency) with aging increase IL-6 level in adventitia and perivascular adipose tissue (PVAT) from adipocytes, fibroblasts, and vascular smooth muscle cells. A locally higher level of IL-6 functions as a chemokine of CD4⁺ T cells to stimulate their differentiation to Th17 cells producing high levels of IL-17, and inhibits them from generating Treg cells, leading to lower IL-10 levels. Increased IL-17/IL-10 ratio in adventitia and PVAT will attract and activate macrophages to produce TNF-α. A sustainable increase in IL-6, IL-17, and TNF-α and a decrease in Treg cells and IL-10 in perivascular settings will trigger an elevation in vascular tone and BP