Comprehensive immune cell analysis of human menstrual-blood-derived stem cells therapy to concanavalin A hepatitis
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 variou...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-09-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.974387/full |
| _version_ | 1811257829180309504 |
|---|---|
| author | Fen Zhang Linxiao Fan Qiuhong Liu Shima Tang Sainan Zhang Sainan Zhang Lanlan Xiao Lingjian Zhang Qian Li Nueraili Maihemuti Lanjuan Li |
| author_facet | Fen Zhang Linxiao Fan Qiuhong Liu Shima Tang Sainan Zhang Sainan Zhang Lanlan Xiao Lingjian Zhang Qian Li Nueraili Maihemuti Lanjuan Li |
| author_sort | Fen Zhang |
| collection | DOAJ |
| description | 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&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+ 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 the liver tissue. The analysis of proinflammatory factors carried out by cytometric bead array demonstrated that tumor necrosis factor alpha (TNF-α), interleukin (IL)-17A, IL-12p70, IL-6, IL-2, IL-1b, and interferon gamma (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 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. |
| first_indexed | 2024-04-12T18:03:37Z |
| format | Article |
| id | doaj.art-c6d54cc255ca48c3ad08345da4643b54 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T18:03:37Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c6d54cc255ca48c3ad08345da4643b542022-12-22T03:22:04ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.974387974387Comprehensive immune cell analysis of human menstrual-blood-derived stem cells therapy to concanavalin A hepatitisFen Zhang0Linxiao Fan1Qiuhong Liu2Shima Tang3Sainan Zhang4Sainan Zhang5Lanlan Xiao6Lingjian Zhang7Qian Li8Nueraili Maihemuti9Lanjuan Li10State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Infectious Disease, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University, Shulan International Medical College, Hangzhou, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaAutoimmune 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&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+ 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 the liver tissue. The analysis of proinflammatory factors carried out by cytometric bead array demonstrated that tumor necrosis factor alpha (TNF-α), interleukin (IL)-17A, IL-12p70, IL-6, IL-2, IL-1b, and interferon gamma (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 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.974387/fullautoimmune hepatitisconcanavalin Amenstrual blood-derived stem cellsCyTOFmesenchymal stem cell therapy |
| spellingShingle | Fen Zhang Linxiao Fan Qiuhong Liu Shima Tang Sainan Zhang Sainan Zhang Lanlan Xiao Lingjian Zhang Qian Li Nueraili Maihemuti Lanjuan Li Comprehensive immune cell analysis of human menstrual-blood-derived stem cells therapy to concanavalin A hepatitis Frontiers in Immunology autoimmune hepatitis concanavalin A menstrual blood-derived stem cells CyTOF mesenchymal stem cell therapy |
| title | Comprehensive immune cell analysis of human menstrual-blood-derived stem cells therapy to concanavalin A hepatitis |
| title_full | Comprehensive immune cell analysis of human menstrual-blood-derived stem cells therapy to concanavalin A hepatitis |
| title_fullStr | Comprehensive immune cell analysis of human menstrual-blood-derived stem cells therapy to concanavalin A hepatitis |
| title_full_unstemmed | Comprehensive immune cell analysis of human menstrual-blood-derived stem cells therapy to concanavalin A hepatitis |
| title_short | Comprehensive immune cell analysis of human menstrual-blood-derived stem cells therapy to concanavalin A hepatitis |
| title_sort | comprehensive immune cell analysis of human menstrual blood derived stem cells therapy to concanavalin a hepatitis |
| topic | autoimmune hepatitis concanavalin A menstrual blood-derived stem cells CyTOF mesenchymal stem cell therapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.974387/full |
| work_keys_str_mv | AT fenzhang comprehensiveimmunecellanalysisofhumanmenstrualbloodderivedstemcellstherapytoconcanavalinahepatitis AT linxiaofan comprehensiveimmunecellanalysisofhumanmenstrualbloodderivedstemcellstherapytoconcanavalinahepatitis AT qiuhongliu comprehensiveimmunecellanalysisofhumanmenstrualbloodderivedstemcellstherapytoconcanavalinahepatitis AT shimatang comprehensiveimmunecellanalysisofhumanmenstrualbloodderivedstemcellstherapytoconcanavalinahepatitis AT sainanzhang comprehensiveimmunecellanalysisofhumanmenstrualbloodderivedstemcellstherapytoconcanavalinahepatitis AT sainanzhang comprehensiveimmunecellanalysisofhumanmenstrualbloodderivedstemcellstherapytoconcanavalinahepatitis AT lanlanxiao comprehensiveimmunecellanalysisofhumanmenstrualbloodderivedstemcellstherapytoconcanavalinahepatitis AT lingjianzhang comprehensiveimmunecellanalysisofhumanmenstrualbloodderivedstemcellstherapytoconcanavalinahepatitis AT qianli comprehensiveimmunecellanalysisofhumanmenstrualbloodderivedstemcellstherapytoconcanavalinahepatitis AT nuerailimaihemuti comprehensiveimmunecellanalysisofhumanmenstrualbloodderivedstemcellstherapytoconcanavalinahepatitis AT lanjuanli comprehensiveimmunecellanalysisofhumanmenstrualbloodderivedstemcellstherapytoconcanavalinahepatitis |