GEOOtherMus musculusOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE224792GEOGSEfalseEpigenetic control of T cells by vitamin C via DNA demethylation [Cut & Tag]Maintenance of T cell naïve (Tn) state and restricting effector T cell differentiation upon basal level stimulations would be critical for immune homeostasis and prevention of autoimmunity. To understand how Tn state is regulated by nutrient cues in a cell-intrinsic manner, here we perform an in vivo CRISPR screening to identify required solute carrier (SLC) proteins that transport metabolites and ions into T cells. Among SLC proteins revealed by this experiment, vitamin C transporter Slc23a2 appears to play a role. Conditional ablation of Slc23a2 in T cells by genetic approaches reduces intracellular vitamin C levels by approximately 80%, accompanied by spontaneous activation and differentiation of Tn cells, autoantibody production, and autoimmune pathology in select organs. Slc23a2-deficient Tn cells exhibit profound DNA hypermethylation, dysregulation of genes controlling signaling transduction and transcription, and enhanced differentiation of helper T cells upon stimulation. These results define a broad regulatory space of vitamin C as a cofactor of Tet enzymes in controlling active DNA demethylation. In agreement, conditional deletion of Tet genes impairs Tn state and increases helper T cell differentiation. Thus, our study reveals a cell-intrinsic mechanism by which micronutrient vitamin C via Slc23a2 maintains Tn state and self-tolerance by promoting Tet-mediated DNA demethylation.2026/05/08GSE224792GSM7032289GSM7032287GSM7032288GSM7032285GSM7032286GSM7032294GSM7032283GSM7032284GSM7032295GSM7032292GSM7032281GSM7032293GSM7032282GSM7032290GSM7032280GSM703229124247224792Mus musculus