Multiple sclerosis (MS) is a chronic autoimmune disease caused by the interaction between environmental factors, such as high dietary salt intake, and genetic risk factors. Regulatory T cells, which suppress an immune response against the body’s own tissue, can malfunction and lead to the development of MS and other autoimmune diseases. A recent study published in Science Translational Medicine identified a shared molecular pathway in regulatory T cells that was altered in individuals with MS and other autoimmune diseases, resulting in reduced suppressive function of these immune cells. The study also found that higher dietary salt intake activates this molecular pathway in regulatory T cells, potentially explaining the link between high salt consumption and autoimmune diseases.
During MS, the immune system attacks myelin, the protective sheath covering nerve fibers, leading to nerve damage and inflammation. Autoimmune diseases involve a malfunction of immune cells including regulatory T cells, which help suppress an autoimmune response. Regulatory T cells are critical in preventing an immune attack against healthy tissue. In individuals with MS, regulatory T cells have been shown to malfunction, reducing their suppressive function. The molecular pathways that cause regulatory T-cell dysfunction are poorly understood, but the recent study uncovered a potential mechanism involving the SGK-1 and PRDM1-S genes. These genes are upregulated by high salt intake, leading to the dysfunction of regulatory T cells and potentially increasing the risk of autoimmune diseases.
The study compared differences in gene expression in regulatory memory T cells from individuals with MS and healthy controls. Researchers found that the PRDM1 gene, which encodes the BLIMP1 protein involved in regulating regulatory T cell function, was overexpressed in MS patients. Additionally, the study found that the PRDM1-S transcript, which regulates BLIMP1 expression, was elevated in memory regulatory T cells from individuals with MS. The expression of SGK-1 was also positively correlated with PRDM1-S expression, suggesting a potential link between these genes in regulatory T cell dysfunction. Further experiments showed that high salt intake led to the activation of the PRDM1-S/SGK-1 pathway in regulatory T cells, contributing to their dysfunction in MS and other autoimmune diseases.
SGK-1, a gene associated with regulatory T-cell dysfunction, inhibits the transcription factor FOXO1, leading to regulatory T-cell dysfunction. High salt intake is linked to an increased risk of autoimmune diseases, including MS, as exposure to high sodium concentrations can interfere with the suppressive function of regulatory T cells by inducing the activation of SGK1. Targeting the PRDM1-S/SGK1 axis in susceptible MS patients could potentially prevent disease onset and progression. Future research may explore PRDM1-S in other cell types, such as those involved in viral infections and cancer progression, as well as developing new therapies for MS based on these findings. Further studies are needed to validate the results and determine the causal role of the PRDM1-S/SGK-1 pathway in MS, as well as to develop effective treatment options for individuals with autoimmune diseases.
