Regulatory T cells in primary sjögren disease: regulatory mechanisms and therapeutic prospects

Primary Sjögren disease (SjD) is a chronic inflammatory autoimmune disorder characterized by lymphocyte proliferation and progressive damage to exocrine glands. Its pathogenesis is complex, and clinical treatment remains challenging. Regulatory T cells (Tregs), a subset of inhibitory T lymphocytes, play a pivotal role in maintaining peripheral immune tolerance and immune homeostasis. They are also critically involved in the pathogenesis and progression of various autoimmune diseases, including SjD. Consequently, modulating the proliferation, activation, and functional balance of Tregs holds significant promise for ameliorating the immune-inflammatory microenvironment in SjD and slowing disease progression. Recent studies have shown that mesenchymal stem cells (MSCs), fenofibrate, and metformin can promote Treg proliferation and improve their function, thereby restoring the Th17/Treg immune balance. These interventions synergistically reduce inflammatory responses, downregulate abnormal immune activation, and alleviate tissue pathological damage, ultimately leading to significantly increased saliva and tear secretion. This review summarizes the regulatory mechanisms of Tregs in SjD based on recent literature and explores the potential of Treg-targeted therapeutic strategies for SjD, aiming to provide a theoretical basis for the development of novel treatment approaches for this disease.