Mesenchymal stem cell transplantation alleviates Sjögren's syndrome symptoms by modulating Tim-3 expression

Mesenchymal stem cell (MSC) transplantation has been proven to be an effective treatment for Sjögren's syndrome (SS) to improve salivary gland pathology and exocrine function, but the mechanism remains unclear. A recently reported inhibitory receptor, TIM-3, also appears to be closely related to autoimmune diseases. Here, we aimed to explore the roles of TIM-3 in the pathogenesis of SS and MSC treatment. The results showed that TIM-3 was downregulated in T cells of SS patients and nonobese diabetic (NOD) mice, which is correlated with SS pathogenesis. MSC transplantation ameliorated SS-like symptoms and pathological changes in the submandibular glands with modulated TIM-3 expression, resulting in attenuation of localized inflammation, fibrosis, and epithelial-mesenchymal transition. Furthermore, TIM-3 is crucial for the inhibitory effect of MSCs on PBMC proliferation in vitro. Therefore, our work has demonstrated that MSC transplantation effectively mitigates the pathological changes of SS by regulating TIM-3 expression, which provides a novel mechanism of MSC treatment and indicates a brand-new perspective of the combination of inhibitory-receptor-targeted treatment and MSC therapy in SS.