AUTHOR=Zhang Fen , Fan Linxiao , Liu Qiuhong , Tang Shima , Zhang Sainan , Xiao Lanlan , Zhang Lingjian , Li Qian , Maihemuti Nueraili , Li Lanjuan 

TITLE=Comprehensive immune cell analysis of human menstrual-blood-derived stem cells therapy to concanavalin A hepatitis

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.974387

DOI=10.3389/fimmu.2022.974387

ISSN=1664-3224

ABSTRACT=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 PBS control (NC) group and ConA injection with or without MenSCs treatment groups, and conventional flow cytometry was used for further validation. The serum ALT, AST levels, and H&E staining depicted that MenSCs treatment could significantly alleviate ConA-induced hepatitis. The 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+ T cells, NKT cells, and PD-L1+ macrophages were notably increased by ConA injection, while MenSCs could decrease ConA-induced macrophage percentage and M1 polarization in liver tissue. The analysis of proinflammatory factors carried out by Cytometric Bead Array demonstrated that TNF-α, IL-17A, IL-12p70, IL-6, IL-2, IL-1b, and IFN-γ 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 liver tissue of ConA-induced hepatitis at 12 hours after ConA injection and found that MenSCs rescued ConA-induced hepatitis mostly by inhibiting macrophages and M1 polarization in mouse liver.