Mesenchymal stem cells alleviate experimental autoimmune cholangitis through immunosuppression and cytoprotective function mediated by galectin-9

• DOI: 10.1186/s13287-018-0979-x
• Publication Date: 2018-09-17T10:48:43Z
• Authors: Junyu Fan; Xiaojun Tang; Qian Wang; Zhuoya Zhang; Shufang Wu; Wenchao Li; Shanshan Liu; Genhong Yao; Hongwei Chen; Lingyun Sun
• Keywords: 0301 basic medicine; Medicine (General); Immunoconjugates; Galectins; QD415-436; Mesenchymal Stem Cell Transplantation; Biochemistry; Autoimmune Diseases; Fatty Acids, Monounsaturated; Immunomodulation; Mice; 03 medical and health sciences; R5-920; Animals; Humans; Galectin-9; Inflammation; Liver Cirrhosis, Biliary; Research; Primary biliary cholangitis; JNK Mitogen-Activated Protein Kinases; Epithelial Cells; Mesenchymal Stem Cells; Serum Albumin, Bovine; Coculture Techniques; 3. Good health; Mice, Inbred C57BL; STAT Transcription Factors; Gene Expression Regulation; Umbilical cord–derived mesenchymal stem cells; Female; Bile Ducts

Mesenchymal stem cells (MSCs) play an anti-inflammatory role by secreting certain bioactive molecules to exert their therapeutic effects for disease treatment. However, the underlying mechanism of MSCs in chronic autoimmune liver diseases—primary biliary cholangitis (PBC), example—remains be elucidated. Human umbilical cord–derived (UC-MSCs) were injected intravenously into 2-octynoic acid coupled bovine serum albumin (2OA-BSA)-induced mice. Serum levels biomarkers and autoantibodies, histologic changes liver, diverse CD4+ T-cell subsets different tissues, chemokine activities analyzed. Moreover, we investigated galectin-9 (Gal-9) expression its function UC-MSCs. In this study, UC-MSC transplantation (UC-MSCT) significantly ameliorated inflammation, primarily diminishing T helper 1 (Th1) Th17 responses as well modifying experimental Mechanistically, UC-MSCs repressed proliferation suppressed differentiation Th1 cells, which was likely dependent on Gal-9. Furthermore, signal transducer activator transcription (STAT) c-Jun N-terminal kinase (JNK) signaling pathways involved production Gal-9 These results suggest that contributes UC-MSC–mediated improve our understanding immunomodulatory mechanisms treatment PBC.