The Role of Sodium in Th17/Treg Immune Dysregulation and Autoimmunity

Autoimmune diseases represent a major and growing health burden, particularly among young adults. Emerging evidence suggests that changes in the environment and diet may contribute to disease. Experimental studies have demonstrated that excessive salt intake can modulate immune function by inducing pathogenic pro-inflammatory T helper 17 cells (Th17) and impairing anti-inflammatory regulatory T cell (Treg) function both in vitro and in vivo, thereby promoting autoimmunity. Serum/glucocorticoid-regulated kinase 1 (SGK1) has been identified as a central mediator of immune function in response to high salt. Additionally, alterations in immunometabolism and epigenetic modulations have been linked to immune dysfunction under high-sodium conditions. Understanding the complex interplay between inflammatory processes, immunometabolism, and epigenetic regulation is essential for deciphering how ionic disturbances may shape T cell immunity and disease. Despite strong evidence from animal models linking sodium intake and shifts in the ionic microenvironment to immunomodulation and disease, evidence from human studies remains limited, largely due to small cohort sizes and methodological constraints. This review provides a comprehensive overview of sodium-induced immune alterations and underscores the need for larger and more standardized clinical studies to further clarify the role of sodium and changes in the ionic microenvironment in autoimmunity.