Review of mechanisms and frontier applications in IL-17A-induced hypertension

Abstract

Background: The immune system is closely related to hypertension. Hypertension is an immune disorder to a certain extent, and inflammation is the basis of abnormally elevated blood pressure (BP). The accumulation of T cells and their cytokines can increase BP and end organ damage. T cells are activated by antigen-presenting cells of the innate immune system or by the influence of a high-sodium diet, the self-environment, or the gut microbiota. These cells produce inflammatory factors and cytokines, such as interleukin-17A (IL-17A) in T helper 17 cells, causing vascular inflammation, hypertension, and target organ damage.

Methods: In this article, we provide an insightful review of the research progress regarding the role of IL-17A in the pathogenesis of hypertension and its effects on different organs while emphasizing the role of IL-17A and its mediated functions in the kidneys, brain, intestines, and vascular system in the development and progression of hypertension.

Results: At the organ level, IL-17A is involved in the development and progression of hypertension in the kidneys, brain, intestines, and blood vessels, interacting with multiple signal pathway.

Conclusions: These findings have significant implications for developing future immunomodulatory therapies, which may lead to the development of potential treatments for hypertension.

Keywords: T helper 17 cells; hypertension; immunity; inflammation; interleukin 17A.

Figure 1

Interaction between IL-17A and other cytokines in renal fibrosis. Naive T-cells develop into Th17 cells under the stimulation of TGF-β and IL-6 and secrete IL-17A. On the other hand, anti-IL-17A or anti-IL-17 receptor A subunit monoclonal antibodies significantly reduced TGF-β levels in renal fibrosis.

Figure 2

Mechanisms of IL-17A-induced hypertension through multiple pathways in the vascular system (a), brain (b), intestinal microbiota (c), and kidneys (d). When the inflammation from gut microbiota gets further into the circulating bloodstream, the brain, autonomic nervous system, and kidneys will be affected.