• The Role of Regulatory T Cells (Tregs) in Immune Homeostasis and Prevention of Inflammatory Diseases
  • Ali Karimi-Jashni,1,*
    1. Department of Cellular and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran


  • Introduction: Regulatory T cells (Tregs) are a specialized subset of CD4+ T lymphocytes characterized by the expression of the transcription factor FOXP3 and surface markers including CD25 and CTLA-4. They are crucial for preserving immune homeostasis by actively suppressing excessive immune responses and maintaining self-tolerance. Two broad categories exist: thymus-derived natural Tregs (nTregs) and peripherally induced Tregs (iTregs), each contributing uniquely to immune regulation. Impairments in Treg quantity or function are intimately linked to the onset and progression of autoimmune diseases such as type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus, in addition to chronic inflammatory conditions like inflammatory bowel disease and asthma.
  • Methods: This review synthesizes key insights gathered from recent preclinical and clinical research focused on Tregs, encompassing molecular markers, suppressive mechanisms, pathological involvement, and therapeutic potential. The analysis integrates data from high-impact immunology journals, prioritizing studies that offer robust mechanistic clarity and translational relevance.
  • Results: Tregs implement immunosuppression via multiple interrelated pathways: secretion of anti-inflammatory cytokines including IL-10, TGF-β, and IL-35; direct downregulation of effector T cell proliferation and cytotoxicity; and modulation of dendritic cell functions primarily through CTLA-4 mediated inhibition of costimulatory molecules CD80/CD86. Additionally, Tregs express high CD25 levels, enabling them to consume IL-2 and thus limit this essential growth factor availability for effector T cells. Tregs display significant phenotypic and functional plasticity driven by environmental cues, which is essential for their adaptability and suppressive potency in varying tissue contexts. In autoimmune diseases, dysfunctional or insufficient Tregs compromise peripheral tolerance, perpetuating inflammation and tissue damage. Therapeutic avenues under active exploration include expansion and adoptive transfer of autologous Tregs, pharmacological modulations like low-dose IL-2 to boost Treg persistence, and gene editing techniques targeting FOXP3 stability to enhance functional longevity. Despite encouraging therapeutic data, maintaining Treg stability in pro-inflammatory environments and avoiding generalized immunosuppression remain critical challenges.
  • Conclusion: Regulatory T cells are key arbiters of immune tolerance and equilibrium, with paramount importance in preventing autoimmune and inflammatory diseases. Expanding our understanding of Tregs’ biology has spurred emergent therapeutic strategies poised to restore immune homeostasis effectively. Future investigations dedicated to enhancing Treg stability, specificity, and safety are imperative to translating these therapies into routine clinical practice, heralding new paradigms in the treatment of immune-mediated conditions.
  • Keywords: Regulatory T cells, Immune homeostasis, Autoimmune diseases, Inflammation, Immunotherapy