Endometrial regenerative cells with galectin-9 high-expression attenuate experimental autoimmune hepatitis

• DOI: 10.1186/s13287-021-02604-2
• Publication Date: 2021-10-15T19:59:22Z
• Authors: Hongda Wang; Yiming Zhao; Bingbing Ren; Yafei Qin; Guangming Li; Dejun Kong; Hong Qin; Jingpeng Hao; Daqing Sun; Hao Wang
• Keywords: 0301 basic medicine; Medicine (General); Research; Galectins; QD415-436; Autoimmune hepatitis; Biochemistry; 3. Good health; Mice, Inbred C57BL; Endometrium; Hepatitis, Autoimmune; Mice; 03 medical and health sciences; R5-920; Animals; Female; Endometrial regenerative cell; Concanavalin A-induced hepatitis; Galectin-9

Abstract Background Autoimmune hepatitis (AIH) is a T cell-mediated immune disease that activates abnormally against hepatic antigens. We have previously reported endometrial regenerative cells (ERCs) were novel source of adult stem cells, which exhibiting with powerful immunomodulatory effects. Galectin-9 (Gal-9) expressed in ERCs and plays an important role regulating cell response. This study aims to explore the attenuation AIH determine potential mechanism Gal-9 ERC-mediated regulation. Methods obtained from menstrual blood healthy female volunteers. In vitro, transfected lentivirus vectors carrying LGALS9 gene encoding green fluoresce protein (GFP-Gal-9-LVs) at MOI 50, expression was detected by ELISA Q-PCR. CD4 + isolated C57BL/6 mouse spleen co-cultured ERCs. The proliferation CCK-8 kit level Lck/zap-70/LAT measured western blot. Furthermore, induced ConA mice randomly assigned untreated, unmodified ERC-treated high-expressing groups. Histopathological score, liver function, /CD8 infiltration tissues, proportion liver, ERC tracking performed accordingly assess progression degree AIH. Results After transfecting GFP-Gal-9-LVs, significantly increased. Additionally, effectively inhibited downregulated active related proteins p-Lck/p-ZAP70/p-LAT vitro. treatment restored ameliorated pathological damage, inhibit CD8 suppress Th1 Th17 response mice. addition, further markedly enhanced IL-10 but reduced levels IFN-γ, TNF-α, IL-4 sera liver. Cell also showed could migrate damaged organs. Conclusions results suggested essential modulator, required attenuating ConA-induced experimental hepatitis. And also, it provides idea for clinical