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SAT0032 Mesenchymal stem cells alleviate experimental autoimmune cholangitis through immunosuppression mediated by galectin-9

Background Mesenchymal stem cells (MSCs) play anti-inflammatory role by secreting some kinds of bioactive molecules. However, the effect of MSCs on chronic autoimmune liver disease, such as primary biliary cholangitis (PBC) and its underlying mechanism remains elusive. Objectives The aim of this study was to assess the efficacy of UC-MSCs treatment (UC-MSCT) in 2OA-BSA-induced murine autoimmune cholangitis and explore its underlying mechanisms. Methods UC-MSCs were transplanted into experimental autoimmune cholangitis mice. Biochemical and histological analysis were performed based on the blood and liver tissues. The immunomodulatory effects of UC-MSCs and its cytoprotective function were also investigated. Results We found that UC-MSCT significantly ameliorated liver inflammation in 2OA-BSA induced autoimmune cholangitis mice, primarily by diminishing Th1 and Th17 responses, and modifying liver chemokine activity. We also found that UC-MSCs significantly repressed the proliferation of CD4 +T cells and suppressed the differentiation of Th1 and Th17 cells, both of which were dependent on galectin-9 (Gal-9). Furthermore, we determined the signal transducer and activator of transcription (STAT) and c-Jun N-terminal kinase (JNK) signalling pathways were involved in the production of Gal-9 in MSCs. Conclusions The present study shows that UC-MSCs exert profound inhibitory effects on inflammatory responses and that they ultimately alleviate the liver injury in experimental autoimmune cholangitis mice. Further, we demonstrate that UC-MSCs inhibit Th1 and Th17 cell responses as well as aberrant chemokine activity through Gal-9 mediated immunosuppression. Additionally, our research reveals that the induction of Gal-9 in MSCs is mediated by the involvement of the STAT and JNK signalling pathways. These findings may help in the development of stem cell therapies for the treatment of PBC. Disclosure of Interest None declared