High-salt diet aggravates allergic rhinitis through the NFAT5 signaling pathway

Allergic rhinitis (AR) affects 10-40% of the world's population, and modern high-salt diets (HSD) may influence immune function. Currently, the influence and mechanism of a HSD on AR remain poorly understood. The study aims to investigate the role of a HSD in AR through the P38/MAPK-NFAT5-SGK1 signaling pathway. The serum IgE levels, 24-hour urinary sodium excretion, and AR symptom scores in patients were detected. To evaluate the immune responses and potential pathway, ovalbumin-induced AR mice were exposed to a HSD. Cellular gene silencing technology was employed to identify key regulators of the NFAT5 pathway. In AR patients, urinary sodium excretion was positively correlated with IgE levels and symptom scores. In the mouse model, a HSD altered the gut microbiota and upregulated NFAT5 expression, leading to nasal mucosal barrier disruption and inflammation exacerbation. Gene-silencing experiments confirmed the critical role of the P38/MAPK-NFAT5-SGK1 pathway in mediating both allergic responses and epithelial damage. Notably, switching from a HSD to a normal diet partially reversed clinical symptoms in mice, but the immune memory remained difficult to reset. In conclusion, this work provides the strong evidence of salt-immune axis in AR through osmotic sensing pathways, advancing mechanistic understanding and clinical management approaches.