The multifaceted impact of a high-salt environment on the immune system and its contribution to salt-sensitive hypertension.

Salt-sensitive hypertension (SSBP) is a common form of hypertension which responds strongly to dietary sodium intake. It is also associated with a significantly higher risk of cardiovascular events and target organ damage. Traditional research has focused on how the vascular, renal and neuroendocrine systems regulate SSBP. However, this study explores the profound effects of a high-salt environment on the immune system and its central role in SSBP pathogenesis, revealing key innovative findings in this field. High salt intake activates multiple key signalling pathways (NF-κB, JAK/STAT, MAPK and the NLRP3 inflammasome) in immune cells, such as antigen-presenting cells, macrophages and Th17 cells, triggering significant oxidative stress and inflammatory cascades. Specific mechanisms include high salt inducing immune cells to perceive sodium ions through the ENaC channel and NCX1, activating the SGK1/FOXO1 axis and NFAT5 to drive Th17/Treg imbalance and the release of pro-inflammatory factors such as IL-6, IL-17A, TNF-α and IL-1β.), excessive ROS production and the resulting protein modifications create new antigens (e.g. IsoLG), and gut microbiota dysbiosis (e.g. reduced Lactobacillus and elevated TMAO) amplifies systemic inflammation by reducing short-chain fatty acids (SCFAs) and increasing endotoxin release, thereby activating TLR4/NF-κB and other pathways. This study emphasises the novel mechanisms by which these signalling pathways NF-κB as the core hub of inflammation; JAK2 in CD11c APC cells; and p38 MAPK in endothelial dysfunction and their interactions drive SSBP. These inflammatory processes impair vascular endothelial function, affect renal sodium excretion and promote renal fibrosis. They also form a vicious cycle with sympathetic nervous system activation, which collectively drives the onset and progression of SSBP. Understanding these immune-mediated inflammatory mechanisms provides an important theoretical basis for developing novel anti-inflammatory therapeutic strategies for SSBP, such as targeting specific signalling pathways or regulating intestinal microbiota.