Transfer of Th17 from Adult Spontaneous Hypertensive Rats Accelerates Development of Hypertension in Juvenile Spontaneous Hypertensive Rats

Jee Young Kim,Eunjo Lee,Soohyeon Koo,Cheong-Wun Kim,Inkyeom Kim,Koichiro Wada

doi:10.1155/2021/6633825

Abstract

Hypertension develops in the recipient rats that are transferred with the activated T helper (Th) 17 cells of the donor rats exposed to high-fructose or high-salt intake. This result suggests that a pathologic Th17 cell plays a role in the development and maintenance of hypertension. Here, we tested the hypothesis that the transfer of Th17 cells from adult spontaneous hypertensive rats (SHR) accelerates the development of hypertension in juvenile SHR. The tail-cuff method was used to measure systolic blood pressure. T cell (Th17 and regulatory T (Treg)) profiling was analyzed by flow cytometry. The expressions of Th17-related interleukin- (IL-) 17A and Treg-related IL-10 were measured by ELISA. Th17 cells isolated from adult SHR were intraperitoneally injected into juvenile recipient SHR and Wistar-Kyoto rats (WKY). SHR exhibited prominent development of hypertension at 15 weeks. The proportion of CD4+IL-17A+ (Th17) cells among Th cells increased whereas the proportion of CD4+FoxP3+ (Treg) cells decreased in SHR, as compared to WKY. The serum levels of IL-17A increased gradually with aging in SHR, but the serum levels of IL-10 did not. The serum levels of IL-17A and IL-10 seemed to be well related to the proportion of Th17 cells and Treg cells, respectively. Injection of Th17 cells isolated from adult SHR accelerates the development of hypertension in juvenile SHR but not in juvenile WKY though it increased the proportion of Th17 cells in juvenile recipient WKY and SHR. The transfer of Th17 cells from adult SHR accelerates the development of hypertension in juvenile SHR. These results implicate that the hypertension in SHR is ascribed to activation of Th17 cells.

Highlights

Hypertension develops in a complex phenomenon of the sympathetic nervous system and the renin-angiotensinaldosterone system
More severe hypertension developed in 10-week-old spontaneous hypertensive rats (SHR) (P < 0:01), whereas normal systolic blood pressure (SBP) were maintained in Wistar-Kyoto rats (WKY) (Supplementary Figure 1a)
This study demonstrates that the transfer of adult the proportion of CD4+IL-17A+ (Th17) cells accelerates the development of hypertension in juvenile SHR

Summary

Introduction

Hypertension develops in a complex phenomenon of the sympathetic nervous system and the renin-angiotensinaldosterone system. It is difficult to restore healthy blood pressure from hypertension by the limitation of the sympathetic nervous system and renin-angiotensin-aldosterone system. Clinical and experimental researches suggest a contribution of immune mechanisms to the development of hypertension [1]. The lack of B and T cells by recombination activating gene-1-knockout (Rag1-/-) mice plays a role in inhibiting immune response and cytokine signaling in high-salt or angiotensin II-induced hypertension [2]. Neutralizing antibodies against IL-17A, IL-17F, or IL-17RA receptor subunits have shown the potential to lower blood pressure and improve hypertension-related end-organ damage [3, 4]. Activation of immune cells in hypertension models is expected to promote the inflammatory response and increase blood pressure [5]

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Discussion

Conclusion