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.