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We have previously reported that endometrial regenerative cells (ERCs) were a novel source of adult stem cells, which exhibiting with powerful immunomodulatory effects. Galectin-9 (Gal-9) is expressed in ERCs and plays an important role in regulating T cell response. This study aims to explore the role of ERCs in attenuation of AIH and to determine the potential mechanism of Gal-9 in ERC-mediated immune regulation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>ERCs were obtained from menstrual blood of healthy female volunteers. In vitro, ERCs were transfected with lentivirus vectors carrying LGALS9 gene and encoding green fluoresce protein (GFP-Gal-9-LVs) at a MOI 50, Gal-9 expression in ERCs was detected by ELISA and Q-PCR. CD4<jats:sup>+<\/jats:sup> T cells isolated from C57BL\/6 mouse spleen were co-cultured with ERCs. The proliferation of CD4<jats:sup>+<\/jats:sup> T cells was detected by CCK-8 kit and the level of Lck\/zap-70\/LAT protein was measured by western blot. Furthermore, AIH was induced by ConA in C57BL\/6 mice which were randomly assigned to untreated, unmodified ERC-treated and Gal-9 high-expressing ERC-treated groups. Histopathological score, liver function, CD4<jats:sup>+<\/jats:sup>\/CD8<jats:sup>+<\/jats:sup> cell infiltration in liver tissues, the proportion of immune cells in the spleen and liver, and ERC tracking were performed accordingly to assess the progression degree of AIH.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>After transfecting with GFP-Gal-9-LVs, Gal-9 expression in ERCs was significantly increased. Additionally, Gal-9 high-expressing ERCs effectively inhibited CD4<jats:sup>+<\/jats:sup> T cell proliferation and downregulated CD4<jats:sup>+<\/jats:sup> T cell active related proteins p-Lck\/p-ZAP70\/p-LAT in vitro. Furthermore, treatment with Gal-9 high-expressing ERCs restored liver function, ameliorated liver pathological damage, inhibit CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cell proliferation and suppress Th1 and Th17 cell response in the hepatitis mice. In addition, Gal-9 high-expressing ERCs further markedly enhanced the level of IL-10 but reduced the levels of IFN-\u03b3, TNF-\u03b1, and IL-4 in mouse sera and liver. Cell tracking also showed that ERCs could migrate to the damaged liver organs.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The results suggested that Gal-9 was an essential modulator, which was required by ERCs in regulating T cell response and attenuating ConA-induced experimental hepatitis. And also, it provides a novel idea for the clinical treatment of AIH.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13287-021-02604-2","type":"journal-article","created":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T19:59:22Z","timestamp":1634327962000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Endometrial regenerative cells with galectin-9 high-expression attenuate experimental autoimmune hepatitis"],"prefix":"10.1186","volume":"12","author":[{"given":"Hongda","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingbing","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yafei","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangming","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dejun","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingpeng","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daqing","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9990-2714","authenticated-orcid":false,"given":"Hao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,15]]},"reference":[{"key":"2604_CR1","doi-asserted-by":"publisher","first-page":"18017","DOI":"10.1038\/nrdp.2018.17","volume":"4","author":"G Mieli-Vergani","year":"2018","unstructured":"Mieli-Vergani G, et al. 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