Attenuation of the severity and changes in the microbiota in an animal model of primary biliary cholangitis by FOXP3− regulatory T cells
Abstract Background Primary biliary cholangitis (PBC), an autoimmune liver disease, presents with progressive damage to the intrahepatic bile ducts with infiltrating mononuclear cells and the appearance of anti‐mitochondrial antibodies (AMAs). The initiation of autoimmune liver disease is permissive...
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| Format: | Article |
| Language: | English |
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Wiley
2023-04-01
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| Series: | Clinical and Translational Discovery |
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| Online Access: | https://doi.org/10.1002/ctd2.187 |
| _version_ | 1827895974734856192 |
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| author | Yi‐Lien Chen Szu‐Ying Chen Ya‐Hui Chuang Bor‐Luen Chiang |
| author_facet | Yi‐Lien Chen Szu‐Ying Chen Ya‐Hui Chuang Bor‐Luen Chiang |
| author_sort | Yi‐Lien Chen |
| collection | DOAJ |
| description | Abstract Background Primary biliary cholangitis (PBC), an autoimmune liver disease, presents with progressive damage to the intrahepatic bile ducts with infiltrating mononuclear cells and the appearance of anti‐mitochondrial antibodies (AMAs). The initiation of autoimmune liver disease is permissively mediated by dysfunctional regulatory T cells (Treg cells). Naïve CD4+ T cells cultured with splenic B220+ cells without additional cytokines or chemicals can differentiate into specific types of Treg cells (Treg/B cells) without expressing forkhead box P3. In this study, we explored the effects of Treg/B cells on disease severity and changes in intestinal microbiota in a murine model of PBC. Methods Treg/B cells were administered to 2‐octenoic acid‐induced PBC mice. Enzyme‐linked immunosorbent assay, flow cytometry and histopathological techniques were used to evaluate the severity of PBC and to assess its therapeutic effect. Diversity of the intestinal microbiota was determined using 16S rRNA sequencing. The suppressive mechanisms of Treg/B cells were investigated using the bone marrow‐derived dendritic cells (BMDCs). Results Treg/B‐cell treatment significantly decreased the levels of serum AMAs against pyruvate dehydrogenase complex E2, lowered the levels of serum bile acids, attenuated inflammatory cell infiltration, reduced dendritic cell activation, altered the population of T cells in the liver and alleviated liver collagen synthesis in PBC mice. In addition, the Treg/B‐cell treatment changed the faecal microbial diversity in PBC mice. Furthermore, Treg/B‐cell treatment decreased the levels of proinflammatory cytokines and expression of costimulatory molecules in BMDCs. This inhibitory effect was partially mediated by the cytotoxic T‐lymphocyte‐associated antigen 4 pathway. Conclusion Treatment with Treg/B cells in a murine model of PBC attenuated liver inflammation and altered the gut microbiota. Immune regulation of Treg/B cells may be a potential therapeutic strategy for treating autoimmune liver disease. |
| first_indexed | 2024-03-12T22:28:19Z |
| format | Article |
| id | doaj.art-13221f93645b492597c232125519cf92 |
| institution | Directory Open Access Journal |
| issn | 2768-0622 |
| language | English |
| last_indexed | 2024-03-12T22:28:19Z |
| publishDate | 2023-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Discovery |
| spelling | doaj.art-13221f93645b492597c232125519cf922023-07-21T18:40:41ZengWileyClinical and Translational Discovery2768-06222023-04-0132n/an/a10.1002/ctd2.187Attenuation of the severity and changes in the microbiota in an animal model of primary biliary cholangitis by FOXP3− regulatory T cellsYi‐Lien Chen0Szu‐Ying Chen1Ya‐Hui Chuang2Bor‐Luen Chiang3Graduate Institute of Clinical Medicine College of Medicine National Taiwan University Taipei TaiwanGraduate Institute of Clinical Medicine College of Medicine National Taiwan University Taipei TaiwanDepartment of Clinical Laboratory Sciences and Medical Biotechnology College of Medicine National Taiwan University Taipei TaiwanGraduate Institute of Clinical Medicine College of Medicine National Taiwan University Taipei TaiwanAbstract Background Primary biliary cholangitis (PBC), an autoimmune liver disease, presents with progressive damage to the intrahepatic bile ducts with infiltrating mononuclear cells and the appearance of anti‐mitochondrial antibodies (AMAs). The initiation of autoimmune liver disease is permissively mediated by dysfunctional regulatory T cells (Treg cells). Naïve CD4+ T cells cultured with splenic B220+ cells without additional cytokines or chemicals can differentiate into specific types of Treg cells (Treg/B cells) without expressing forkhead box P3. In this study, we explored the effects of Treg/B cells on disease severity and changes in intestinal microbiota in a murine model of PBC. Methods Treg/B cells were administered to 2‐octenoic acid‐induced PBC mice. Enzyme‐linked immunosorbent assay, flow cytometry and histopathological techniques were used to evaluate the severity of PBC and to assess its therapeutic effect. Diversity of the intestinal microbiota was determined using 16S rRNA sequencing. The suppressive mechanisms of Treg/B cells were investigated using the bone marrow‐derived dendritic cells (BMDCs). Results Treg/B‐cell treatment significantly decreased the levels of serum AMAs against pyruvate dehydrogenase complex E2, lowered the levels of serum bile acids, attenuated inflammatory cell infiltration, reduced dendritic cell activation, altered the population of T cells in the liver and alleviated liver collagen synthesis in PBC mice. In addition, the Treg/B‐cell treatment changed the faecal microbial diversity in PBC mice. Furthermore, Treg/B‐cell treatment decreased the levels of proinflammatory cytokines and expression of costimulatory molecules in BMDCs. This inhibitory effect was partially mediated by the cytotoxic T‐lymphocyte‐associated antigen 4 pathway. Conclusion Treatment with Treg/B cells in a murine model of PBC attenuated liver inflammation and altered the gut microbiota. Immune regulation of Treg/B cells may be a potential therapeutic strategy for treating autoimmune liver disease.https://doi.org/10.1002/ctd2.187faecal microbiotaprimary biliary cholangitistherapeutic effectTreg/B cellsTregs |
| spellingShingle | Yi‐Lien Chen Szu‐Ying Chen Ya‐Hui Chuang Bor‐Luen Chiang Attenuation of the severity and changes in the microbiota in an animal model of primary biliary cholangitis by FOXP3− regulatory T cells Clinical and Translational Discovery faecal microbiota primary biliary cholangitis therapeutic effect Treg/B cells Tregs |
| title | Attenuation of the severity and changes in the microbiota in an animal model of primary biliary cholangitis by FOXP3− regulatory T cells |
| title_full | Attenuation of the severity and changes in the microbiota in an animal model of primary biliary cholangitis by FOXP3− regulatory T cells |
| title_fullStr | Attenuation of the severity and changes in the microbiota in an animal model of primary biliary cholangitis by FOXP3− regulatory T cells |
| title_full_unstemmed | Attenuation of the severity and changes in the microbiota in an animal model of primary biliary cholangitis by FOXP3− regulatory T cells |
| title_short | Attenuation of the severity and changes in the microbiota in an animal model of primary biliary cholangitis by FOXP3− regulatory T cells |
| title_sort | attenuation of the severity and changes in the microbiota in an animal model of primary biliary cholangitis by foxp3 regulatory t cells |
| topic | faecal microbiota primary biliary cholangitis therapeutic effect Treg/B cells Tregs |
| url | https://doi.org/10.1002/ctd2.187 |
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