Immune Dysregulation Orchestrated by High-Salt Diet: Mechanistic Insights into Disease Pathogenesis

Li Chen,1,2 Xi-Le Peng,1,2 Zhi-Xuan Chen,1,2 Lu-Ming Qi,1,2 Ting-Ting Deng,2,3 Li-Na Xia1,2 1School of Health Preservation and Rehabilitation, Chengdu University of TCM, Chengdu, Sichuan, People’s Republic of China; 2Key Laboratory of Traditional Chinese Medicine Regimen and Health Industry Development, State Administration of TCM, Chengdu, Sichuan, People’s Republic of China; 3School of Nursing, Chengdu University of TCM, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Li-Na Xia, School of Health Preservation and Rehabilitation, Chengdu University of TCM, Chengdu, Sichuan, People’s Republic of China, Email xialina@cdutcm.edu.cnBackground: Excessive salt consumption has been associated with detrimental health consequences, including hypertension, colitis, and autoimmune disorders. However, recent studies have proposed that high salt diet (HSD) can both stimulate the immune system, affecting the differentiation of immune cells, promoting or inhibiting cytokine secretion to fight cancer or elicit a more potent autoimmune response, and exerting an immunosuppressive effect to influence disease development, providing mechanistic insights into the direction of immune regulation in which HSD affects disease.Objective: This paper reviews the immunomodulatory effects of HSD on various innate immune and adaptive cells, especially macrophages, dendritic cells, and T cells, in relation to disease development.Methods: We identified papers by electronically searching the Web of Science (WOS) database from inception through March 2023.Results: A growing number of animal experiments and in vitro cell culture studies have shown that HSD can regulate the differentiation and activation of a variety of immune cells, and promote or inhibit different cytokines to mediate the development of a variety of diseases, including nephropathy, hypertension, cancer, inflammatory bowel disease, and a number of autoimmune diseases. These findings provide a new mechanism for pathological changes in the direction of immune regulation and suggest that HSD is a predisposing factor for a variety of diseases, providing new mechanistic insights into dietary health modification.Conclusion: HSD mediates the development of multiple diseases by regulating the differentiation and activation of a variety of immune cells, and the underlying mechanisms may be related to gut microbes and their metabolites.Keywords: HSD, immune dysregulation, disease pathogenesis, mechanistic insights, review