Autoimmune thyroid diseases (AITDs), including Hashimoto's thyroiditis and Graves' disease, arise from thyroid-specific autoimmunity driven by a breakdown of immune tolerance and dysregulated T-cell responses. Within this immune network, imbalance between T helper 17 (Th17) cells and regulatory T (Treg) cells has emerged as a major determinant of persistent inflammation and defective immune restraint. These two subsets are supported by distinct but interconnected metabolic programs. Th17 cells preferentially engage glycolytic and anabolic pathways to sustain inflammatory activity, whereas Treg cells rely more strongly on oxidative metabolism and mitochondrial fitness to preserve lineage stability and suppressive function. In AITDs, these intracellular programs are further reshaped by disease-associated microenvironmental cues, including excess iodine, oxidative stress, lactate accumulation, inflammatory cytokines, and tissue-derived stromal signals. This review summarizes how glucose, lipid, mitochondrial, and amino acid metabolism collectively regulate Th17 and Treg differentiation and function. We further examine how these pathways are altered in AITDs and distorted in thyroid and orbital tissues to amplify immune disequilibrium. Finally, we discuss emerging therapeutic strategies aimed at targeting immune metabolic circuits to restore immune homeostasis.
Zhou et al. (2026) studied this question.