Dietary caloric restriction protects experimental autoimmune uveitis by regulating Teff/Treg balance

Uveitis, an autoimmune disease, often leads to blindness. CD4⁺ T cells, including regulatory T cells (Tregs) and effector T cells (Th1 and Th17), play a critical role in its pathogenesis. Caloric restriction (CR) has been shown to alleviate autoimmune diseases. However, careful characterization of the impact of CR on experimental autoimmune uveitis (EAU) is poorly understood. This study used single-cell RNA sequencing to analyze cervical draining lymph nodes in mice under ad libitum (AL) and CR diets, with or without EAU. CR increased Tregs, altered immune cell metabolism, reduced EAU symptoms, and downregulated inflammatory and glycolysis genes. Flow cytometry confirmed CR's inhibitory effect on Th1 and Th17 proliferation and its promotion of Treg proliferation. CR also balanced CD4⁺ T cells by inhibiting the PI3K/AKT/c-Myc pathway and reducing GM-CSF in Th17 cells. These findings suggest CR as a potential therapeutic strategy for autoimmune diseases.