Aberrant Nutrient Metabolism in T Cells: Pathogenesis Insight and Therapeutic Target for Autoimmune Diseases

Abnormal T-cell activation and differentiation are pivotal in the pathogenesis of autoimmune disorders. Traditionally, T cell activation is orchestrated by three canonical signals: antigen recognition through the T-cell receptor (TCR) and major histocompatibility complex (MHC) interaction, co-stimulatory signals, and cytokine signaling. Recent studies have highlighted nutrients as a key fourth signal in modulating T cell immunity. T cell metabolism is integral to regulating cell proliferation, survival, and differentiation. Dysregulation of nutrient metabolism, including glucose, amino acids, and lipids, has been considered a crucial determinant of T cell activation, differentiation, and function, and may lead to the disease progression of autoimmune disorders, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS). This review aims to elucidate the impact of T cell metabolic reprogramming on autoimmune disease development and explore potential therapeutic approaches targeting nutrient metabolism for treating autoimmune disorders.