Targeting glutamine metabolism in CD4⁺ T-cell-mediated autoimmune diseases

CD4⁺ T cells play a vital role in the occurrence and development of autoimmune diseases (AID). The differentiation direction and function of CD4⁺ T cells are both regulated by metabolic reprogramming, which differs across various CD4⁺ T subsets. Glutamine (Gln), as an immunoregulatory nutrient, not only provides bioenergy and biosynthesis for the differentiation and effector function of CD4⁺ T cells but also regulates intracellular redox conditions and produces metabolic intermediates that are used for epigenetic modification of effector cell genes. Here, we review the metabolic characteristics of Gln in CD4⁺ T cells and its regulatory effects on CD4⁺ T-cell differentiation and function. We also summarize potential targets on Gln metabolism for AID therapy, including Gln transporters, Gls1, GSH synthesis and epigenetic modification. However, the primary challenge remains how to achieve cell type-specific metabolic inhibition in vivo. Therefore, future research should focus on developing selective and effective therapeutic agents that modulate Gln metabolism while minimizing cytotoxicity for AID treatment.