Single-cell RNA sequencing reveals that a high salt diet increases IL6R-JAK1-STAT3 gene signaling pathway activity in intestinal B cells and Tfh cells of salt-sensitive hypertension animal model.

Although the immune system plays a crucial role in hypertension, its underlying mechanisms remain unclear. While extensive research has explored the gut-immune relationship in various diseases, the role of gut immunity in salt-sensitive (SS) hypertension is not well understood. In this study, we aimed to elucidate the role of gut immunity in the development of SS hypertension by analyzing immune cells in the gut and blood using single-cell RNA sequencing (scRNA-seq). Six-week-old Dahl SS rats were fed either a normal salt diet (NSD; 0.4% NaCl) or a high-salt diet (HSD; 4% NaCl) for four weeks. Blood pressure was measured weekly using the tail-cuff method. After four weeks, small intestine lamina propria cells (SILPs) and peripheral blood mononuclear cells (PBMCs) were isolated and subjected to scRNA-seq. Our results demonstrated an increase in gut B and T follicular helper (Tfh)-like cells in SS rats. Furthermore, KEGG pathway analysis revealed that HSD upregulated IL-6 receptor (IL-6R)-JAK-STAT signaling in B cells and Tfh-like cells. These findings provide novel insights into the potential of targeting the gut immunity in the treatment of SS hypertension.