A High-Salt Diet Disturbs the Development and Function of Natural Killer Cells in Mice.

Xiaokang Zeng,Weibiao Lv,Yan Li,Liming Zeng,Zibo Wei,Chong Zeng,Yanning Ma,Xu Lin,Qiang Xiao,Xinhuai Dong,Zhipeng Xu

doi:10.1155/2020/6687143

Xiaokang Zeng, Weibiao Lv + Show 9 more

Open Access

https://doi.org/10.1155/2020/6687143

Copy DOI

Abstract

A high-salt diet (HSD) is common worldwide and can lead to cardiovascular disease, chronic inflammation, and autoimmune diseases. Moreover, increasing evidence shows that HSD is closely related to a variety of immune diseases. Natural killer (NK) cells are important innate immune cells that directly kill their targets via degranulation and secretion of interferon gamma (IFN-γ). NK cells play a vital role in resisting viruses and preventing the malignant transformation of cells; however, whether HSD affects the development and function of NK cells has not yet been elucidated. Therefore, the purpose of the present study was to understand the effects of HSD on the development and function of NK cells, in addition to investigating the underlying molecular mechanism. Our results show that the number of NK cells in the spleen and lungs of HSD-fed mice was significantly reduced, which may be due to the inhibition of NK cell proliferation. Further, the development of NK cells in mice was evaluated, and it was found that HSD reduced the effective NK cell subset (CD27+CD11b−). Moreover, it was also found that the ability of NK cells to secrete CD107a and IFN-γ in HSD-fed mice was decreased following stimulation with RMA-S and YAC-1 tumor cells. Finally, the underlying molecular mechanism was evaluated, and it was found that HSD increased the production of reactive oxygen species (ROS) by NK cells, while the expression of CD122 was decreased, suggesting that HSD downregulates CD122 expression in NK cells via ROS signaling, thereby reducing the responsiveness to IL-15 and ultimately inhibiting NK cell function. The present research discovered a novel mechanism by which HSD inhibits the function of NK cells, providing an alternative avenue for the treatment of immune diseases caused by HSD.

Highlights

Natural killer (NK) cells are a type of lymphocyte that develop from hematopoietic stem cells in the bone marrow
Ki67 is an essential indicator of cell proliferation, and we found that the proliferation of NK cells in the spleen of high-salt diet (HSD)-fed mice was significantly inhibited
We found that reactive oxygen species (ROS) production in NK cells from the spleen of HSD-fed mice was significantly increased in comparison with that in control mice, indicating that the oxidative stress level of NK cells from HSD-fed mice was increased (Figure 7(d)), which will affect the expression of important signaling molecules and subsequently impact signal transduction

Summary

Introduction

Natural killer (NK) cells are a type of lymphocyte that develop from hematopoietic stem cells in the bone marrow. NK cells continuously acquire functional receptors and gradually mature [1], eventually directly destroying pathogen-infected or transformed cells and playing an important role in innate immunity [2]. NK cells play a crucial role in innate immunity, their differentiation mechanisms remain poorly understood. Increasing evidence shows that HSD weakens the immune system and promotes the development of hypertension by stimulating proinflammatory T cells [11]. High-dose salt treatment promotes the differentiation of follicular T helper cells (Tfh), accelerating the development of lupus syndrome in mice [13]; whether HSD affects the development and function of NK cells remains unclear

Objectives

Methods

Conclusion