{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:15:11Z","timestamp":1787026511182,"version":"build-2736575974"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T00:00:00Z","timestamp":1664409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Autoimmune hepatitis is an autoimmune disease with increasing occurrence worldwide. The most common and convenient mouse model is the concanavalin A (ConA) mouse model. Human menstrual-blood-derived stem cells (MenSCs) have shown great potential as a type of mesenchymal stem cell for treating various diseases. Time-of-flight mass cytometry was performed in phosphate-buffered saline control (NC) group and ConA injection with or without MenSCs treatment groups, and conventional flow cytometry was used for further validation. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and H&amp;amp;E staining depicted that MenSCs treatment could significantly alleviate ConA-induced hepatitis. The t-distributed stochastic neighbor embedding (t-SNE) analysis of nine liver samples displayed favorable cell clustering, and the NC group was significantly different from the other two groups. The proportions of CD69\n                    <jats:sup>+<\/jats:sup>\n                    T cells, NKT cells, and PD-L1\n                    <jats:sup>+<\/jats:sup>\n                    macrophages were notably increased by ConA injection, while MenSCs could decrease ConA-induced macrophage percentage and M1 polarization in the liver tissue. The analysis of proinflammatory factors carried out by cytometric bead array demonstrated that tumor necrosis factor alpha (TNF-\u03b1), interleukin (IL)-17A, IL-12p70, IL-6, IL-2, IL-1b, and interferon gamma (IFN-\u03b3) were upregulated after ConA injection and then rapidly decreased at 12 h. MenSCs also played an important role in downregulating these cytokines. Here, we described the comprehensive changes in leukocytes in the liver tissue of ConA-induced hepatitis at 12 h after ConA injection and found that MenSCs rescued ConA-induced hepatitis mostly by inhibiting macrophages and M1 polarization in mouse liver.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2022.974387","type":"journal-article","created":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T13:00:31Z","timestamp":1664456431000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Comprehensive immune cell analysis of human menstrual-blood-derived stem cells therapy to concanavalin A hepatitis"],"prefix":"10.3389","volume":"13","author":[{"given":"Fen","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linxiao","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuhong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shima","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sainan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanlan","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingjian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nueraili","family":"Maihemuti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanjuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.13342","article-title":"Increase trend in the prevalence and Male-to-Female ratio of primary biliary cholangitis, autoimmune hepatitis, and primary sclerosing cholangitis in Japan","volume":"49","author":"Tanaka","year":"2019","journal-title":"Hepatol Res"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14480","article-title":"Incidence, prevalence and mortality of autoimmune hepatitis in England 1997-2015","volume":"40","author":"Gr\u00f8nbaek","year":"2020","journal-title":"A Population-Based Cohort Study Liver Int"},{"key":"B3","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.hbpd.2019.08.004","article-title":"Acute onset of autoimmune hepatitis in children and adolescents","volume":"19","author":"Smolka","year":"2020","journal-title":"Hepatobil Pancreat Dis Int"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.14.3306","article-title":"Aetiopathogenesis of autoimmune hepatitis","volume":"14","author":"Vergani","year":"2008","journal-title":"World J Gastroenterol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"18017","DOI":"10.1038\/nrdp.2018.17","article-title":"Autoimmune hepatitis","volume":"4","author":"Mieli-Vergani","year":"2018","journal-title":"Nat Rev Dis Primers"},{"key":"B6","doi-asserted-by":"publisher","first-page":"58","DOI":"10.3350\/cmh.2020.0189","article-title":"Recent updates on the management of autoimmune hepatitis","volume":"27","author":"Komori","year":"2021","journal-title":"Clin Mol Hepatol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)62163-1","article-title":"Autoimmune hepatitis","volume":"382","author":"Heneghan","year":"2013","journal-title":"Lancet (London England)"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.12.032","article-title":"Mycophenolate for the treatment of autoimmune hepatitis: Prospective assessment of its efficacy and safety for induction and maintenance of remission in a Large cohort of treatment-na\u00efve patients","volume":"55","author":"Zachou","year":"2011","journal-title":"J Hepatol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v25.i41.6190","article-title":"Therapeutic potential of menstrual blood stem cells in treating acute liver failure","volume":"25","author":"Cen","year":"2019","journal-title":"World J Gastroenterol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2017.08.022","article-title":"Comparative restoration of acute liver failure by menstrual blood stem cells compared with bone marrow stem cells in mice model","volume":"19","author":"Fathi-Kazerooni","year":"2017","journal-title":"Cytotherapy"},{"key":"B11","article-title":"Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues","volume":"6","author":"Friedenstein","year":"1968","journal-title":"Transplantation"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-05-1670","article-title":"Isolation of multipotent mesenchymal stem cells from umbilical cord blood","volume":"103","author":"Lee","year":"2004","journal-title":"Blood"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-10-56","article-title":"Therapeutic potential of transplanted placental mesenchymal stem cells in treating Chinese miniature pigs with acute liver failure","volume":"10","author":"Cao","year":"2012","journal-title":"BMC Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1089\/107632701300062859","article-title":"Multilineage cells from human adipose tissue: Implications for cell-based therapies","volume":"7","author":"Zuk","year":"2001","journal-title":"Tissue Eng"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-5-57","article-title":"Endometrial regenerative cells: A novel stem cell population","volume":"5","author":"Meng","year":"2007","journal-title":"J Transl Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2013.0390","article-title":"Transplantation of human menstrual blood progenitor cells improves hyperglycemia by promoting endogenous progenitor differentiation in type 1 diabetic mice","volume":"23","author":"Wu","year":"2014","journal-title":"Stem Cells Dev"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2015-0265","article-title":"Human menstrual blood-derived stem cells ameliorate liver fibrosis in mice by targeting hepatic stellate cells via paracrine mediators","volume":"6","author":"Chen","year":"2017","journal-title":"Stem Cells Trans Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00140","article-title":"Transplantation of human menstrual blood-derived mesenchymal stem cells alleviates alzheimer\u2019s disease-like pathology in App\/Ps1 transgenic mice","volume":"11","author":"Zhao","year":"2018","journal-title":"Front Mol Neurosci"},{"key":"B19","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1186\/s13287-019-1243-8","article-title":"Genome-wide DNA methylation and hydroxymethylation analysis reveal human menstrual blood-derived stem cells inhibit hepatocellular carcinoma growth through oncogenic pathway suppression Via regulating 5-hmc in enhancer elements","volume":"10","author":"Wu","year":"2019","journal-title":"Stem Cell Res Ther"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12962","article-title":"Ipsc-derived mesenchymal stem cells exert scf-dependent recovery of cigarette smoke-induced Apoptosis\/Proliferation imbalance in airway cells","volume":"21","author":"Li","year":"2017","journal-title":"J Cell Mol Med"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/4915149","article-title":"Fgf21 mediates mesenchymal stem cell senescence Via regulation of mitochondrial dynamics","volume":"2019","author":"Li","year":"2019","journal-title":"Oxid Med Cell Longev"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2638","article-title":"Human ipsc-Msc-Derived xenografts modulate immune responses by inhibiting the cleavage of caspases","volume":"35","author":"Li","year":"2017","journal-title":"Stem Cells"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.575572","article-title":"Regulatory T cells in autoimmune hepatitis: Unveiling their roles in mouse models and patients","volume":"11","author":"Wang","year":"2020","journal-title":"Front Immunol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s13287-022-02734-1","article-title":"Human menstrual blood-derived stem cell transplantation suppresses liver injury in ddc-induced chronic cholestasis","volume":"13","author":"Yang","year":"2022","journal-title":"Stem Cell Res Ther"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1159\/000489074","article-title":"Comparison of concanavalin a-induced murine autoimmune hepatitis models","volume":"46","author":"Ye","year":"2018","journal-title":"Cell Physiol Biochem"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201646837","article-title":"Cd69: From activation marker to metabolic gatekeeper","volume":"47","author":"Cibri\u00e1n","year":"2017","journal-title":"Eur J Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20060772","article-title":"Cd127 expression inversely correlates with Foxp3 and suppressive function of human Cd4+ T reg cells","volume":"203","author":"Liu","year":"2006","journal-title":"J Exp Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.108411","article-title":"Pathogenesis of concanavalin a induced autoimmune hepatitis in mice","volume":"102","author":"Hao","year":"2022","journal-title":"Int Immunopharmacol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.Cir-17-0537","article-title":"Programmed cell death ligand 1 (Pd-L1) signaling regulates macrophage proliferation and activation","volume":"6","author":"Hartley","year":"2018","journal-title":"Cancer Immunol Res"},{"key":"B30","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1172\/jci115836","article-title":"A T cell-dependent experimental liver injury in mice inducible by concanavalin a","volume":"90","author":"Tiegs","year":"1992","journal-title":"J Clin Invest"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v18.i2.119","article-title":"Immune mechanisms of concanavalin a model of autoimmune hepatitis","volume":"18","author":"Wang","year":"2012","journal-title":"World J Gastroenterol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2004.08.012","article-title":"Osteopontin as a mediator of nkt cell function in T cell-mediated liver diseases","volume":"21","author":"Diao","year":"2004","journal-title":"Immunity"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01881","article-title":"Quantitative proteomic analysis reveals that arctigenin alleviates concanavalin a-induced hepatitis through suppressing immune system and regulating autophagy","volume":"9","author":"Feng","year":"2018","journal-title":"Front Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00758","article-title":"Nod-like receptor protein 3 inflammasome-dependent il-1 beta accelerated cona-induced hepatitis","volume":"9","author":"Luan","year":"2018","journal-title":"Front Immunol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"4032484","DOI":"10.1155\/2018\/4032484","article-title":"The protective effects of levo-tetrahydropalmatine on cona-induced liver injury are Via Traf6\/Jnk signaling","author":"Yu","year":"2018","journal-title":"Mediators Inflammation"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.21813","article-title":"Cqmuh-011 mitigates autoimmune hepatitis Via inhibiting the function of T lymphocytes","volume":"82","author":"Ling","year":"2021","journal-title":"Drug Dev Res"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2007.02.002","article-title":"Aging affects initiation and continuation of T cell proliferation","volume":"128","author":"Jiang","year":"2007","journal-title":"Mech Ageing Dev"},{"key":"B38","article-title":"Secoemestrin c inhibits activation of Nkt\/Conventional T cells and protects against concanavalin a-induced autoimmune hepatitis in mice","volume":"12","author":"Tan","year":"2020","journal-title":"Am J Transl Res"},{"key":"B39","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.150.2.673","article-title":"Aberrant expression of the very early activation antigen on Mrl\/Mp-Lpr\/Lpr lymphocytes","volume":"150","author":"Sobel","year":"1993","journal-title":"J Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22561","article-title":"Superoxide produced by kupffer cells is an essential effector in concanavalin a-induced hepatitis in mice","volume":"48","author":"Nakashima","year":"2008","journal-title":"Hepatology"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/s0002-9440(10)64804-3","article-title":"Importance of kupffer cells for T-Cell-Dependent liver injury in mice","volume":"157","author":"Sch\u00fcmann","year":"2000","journal-title":"Am J Pathol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-3584-0_17","article-title":"Directed differentiation of human-induced pluripotent stem cells to mesenchymal stem cells","volume":"1416","author":"Lian","year":"2016","journal-title":"Methods Mol Biol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-1050-x","article-title":"Production, safety and efficacy of ipsc-derived mesenchymal stromal cells in acute steroid-resistant graft versus host disease: A phase I, multicenter, open-label, dose-escalation study","volume":"26","author":"Bloor","year":"2020","journal-title":"Nat Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.974387\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T22:14:12Z","timestamp":1676931252000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.974387\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,29]]},"references-count":43,"alternative-id":["10.3389\/fimmu.2022.974387"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.974387","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,29]]},"article-number":"974387"}}