Regulatory T Cells in Immune Homeostasis: Mechanisms of Peripheral Tolerance and Immunoregulation

Regulatory T cells (Tregs) are specialized subsets of T lymphocytes that maintain immune tolerance, suppress excessive immune responses, and preserve immune homeostasis. These cells are essential for preventing autoimmunity, controlling inflammation, and modulating immune responses during infection, cancer, and transplantation. The transcription factor Forkhead box P3 (FOXP3) serves as the master regulator of Treg development and function, while cytokines such as interleukin-10 (IL-10), transforming growth factor-beta (TGF-β), and interleukin-35 (IL-35) mediate their suppressive activities. Recent advances have revealed substantial heterogeneity among Treg populations, including thymus-derived and peripheral Tregs, tissue-resident Tregs, and memory-like Tregs. Dysregulation of Treg number or function contributes significantly to autoimmune diseases, chronic inflammatory conditions, infections, and tumor progression. Furthermore, emerging therapeutic approaches targeting Tregs, including low-dose IL-2 therapy and chimeric antigen receptor Treg (CAR-Treg) therapy, are gaining clinical importance. This review discusses the biology, classification, molecular mechanisms, suppressive pathways, and clinical significance of Tregs in immune homeostasis and disease.