Cyclosporine A Regulates Influenza A Virus-induced Macrophages Polarization and Inflammatory Responses by Targeting Cyclophilin A
Cyclosporine A (CsA) is an immunosuppressive drug that suppresses T cell responses and is broadly used in transplantation. Its immunosuppressive action is closely linked to its binding of cyclophilin A (CypA), which widely distributed in different cell types. CsA also regulates the functions of inna...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.861292/full |
| _version_ | 1828731354359005184 |
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| author | Xiaoyuan Bai Xiaoyuan Bai Wenxian Yang Wenxian Yang Heqiao Li Heqiao Li Yuna Zhao Yuna Zhao Wenhui Fan He Zhang Wenjun Liu Wenjun Liu Wenjun Liu Wenjun Liu Lei Sun Lei Sun |
| author_facet | Xiaoyuan Bai Xiaoyuan Bai Wenxian Yang Wenxian Yang Heqiao Li Heqiao Li Yuna Zhao Yuna Zhao Wenhui Fan He Zhang Wenjun Liu Wenjun Liu Wenjun Liu Wenjun Liu Lei Sun Lei Sun |
| author_sort | Xiaoyuan Bai |
| collection | DOAJ |
| description | Cyclosporine A (CsA) is an immunosuppressive drug that suppresses T cell responses and is broadly used in transplantation. Its immunosuppressive action is closely linked to its binding of cyclophilin A (CypA), which widely distributed in different cell types. CsA also regulates the functions of innate immune cells, but the mechanism remains elusive. Here, we investigate the role of CsA in regulating macrophages polarization in influenza A virus-infected mice and mouse bone marrow-derived macrophages. CsA downregulates pro-inflammatory cytokines expression and upregulates anti-inflammatory cytokines expression. Mechanically, CsA decreases the polarization of macrophages into pro-inflammatory M1 phenotype and increases the polarization of macrophages into anti-inflammatory M2 phenotype. Further studies show that CsA regulates macrophages polarization-associated IFN-γ/STAT1 and IL-4/STAT6 signaling pathways. Meanwhile, all these roles of CsA are eliminated when CypA is absent, suggesting that CsA regulates macrophages polarization and inflammatory responses depend on its binding to CypA. Collectively, these results reveal a crucial mechanism of CsA in attenuating IAV-induced inflammatory responses by a switch in macrophages polarization. |
| first_indexed | 2024-04-12T17:43:51Z |
| format | Article |
| id | doaj.art-fafc37d1dca0450b88afcce871b41ceb |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T17:43:51Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-fafc37d1dca0450b88afcce871b41ceb2022-12-22T03:22:43ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-05-011310.3389/fimmu.2022.861292861292Cyclosporine A Regulates Influenza A Virus-induced Macrophages Polarization and Inflammatory Responses by Targeting Cyclophilin AXiaoyuan Bai0Xiaoyuan Bai1Wenxian Yang2Wenxian Yang3Heqiao Li4Heqiao Li5Yuna Zhao6Yuna Zhao7Wenhui Fan8He Zhang9Wenjun Liu10Wenjun Liu11Wenjun Liu12Wenjun Liu13Lei Sun14Lei Sun15CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, ChinaInstitute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, ChinaInstitute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, ChinaSavaid Medical School, University of Chinese Academy of Sciences, Beijing, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, ChinaState Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources & Laboratory of Animal Infectious Diseases, College of Animal Sciences and Veterinary Medicine, Guangxi University, Nanning, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, ChinaInstitute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, ChinaInstitute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, ChinaSavaid Medical School, University of Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources & Laboratory of Animal Infectious Diseases, College of Animal Sciences and Veterinary Medicine, Guangxi University, Nanning, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, ChinaSavaid Medical School, University of Chinese Academy of Sciences, Beijing, ChinaCyclosporine A (CsA) is an immunosuppressive drug that suppresses T cell responses and is broadly used in transplantation. Its immunosuppressive action is closely linked to its binding of cyclophilin A (CypA), which widely distributed in different cell types. CsA also regulates the functions of innate immune cells, but the mechanism remains elusive. Here, we investigate the role of CsA in regulating macrophages polarization in influenza A virus-infected mice and mouse bone marrow-derived macrophages. CsA downregulates pro-inflammatory cytokines expression and upregulates anti-inflammatory cytokines expression. Mechanically, CsA decreases the polarization of macrophages into pro-inflammatory M1 phenotype and increases the polarization of macrophages into anti-inflammatory M2 phenotype. Further studies show that CsA regulates macrophages polarization-associated IFN-γ/STAT1 and IL-4/STAT6 signaling pathways. Meanwhile, all these roles of CsA are eliminated when CypA is absent, suggesting that CsA regulates macrophages polarization and inflammatory responses depend on its binding to CypA. Collectively, these results reveal a crucial mechanism of CsA in attenuating IAV-induced inflammatory responses by a switch in macrophages polarization.https://www.frontiersin.org/articles/10.3389/fimmu.2022.861292/fullinfluenza A virusmacrophages polarizationcyclosporine Acyclophilin Ainflammation |
| spellingShingle | Xiaoyuan Bai Xiaoyuan Bai Wenxian Yang Wenxian Yang Heqiao Li Heqiao Li Yuna Zhao Yuna Zhao Wenhui Fan He Zhang Wenjun Liu Wenjun Liu Wenjun Liu Wenjun Liu Lei Sun Lei Sun Cyclosporine A Regulates Influenza A Virus-induced Macrophages Polarization and Inflammatory Responses by Targeting Cyclophilin A Frontiers in Immunology influenza A virus macrophages polarization cyclosporine A cyclophilin A inflammation |
| title | Cyclosporine A Regulates Influenza A Virus-induced Macrophages Polarization and Inflammatory Responses by Targeting Cyclophilin A |
| title_full | Cyclosporine A Regulates Influenza A Virus-induced Macrophages Polarization and Inflammatory Responses by Targeting Cyclophilin A |
| title_fullStr | Cyclosporine A Regulates Influenza A Virus-induced Macrophages Polarization and Inflammatory Responses by Targeting Cyclophilin A |
| title_full_unstemmed | Cyclosporine A Regulates Influenza A Virus-induced Macrophages Polarization and Inflammatory Responses by Targeting Cyclophilin A |
| title_short | Cyclosporine A Regulates Influenza A Virus-induced Macrophages Polarization and Inflammatory Responses by Targeting Cyclophilin A |
| title_sort | cyclosporine a regulates influenza a virus induced macrophages polarization and inflammatory responses by targeting cyclophilin a |
| topic | influenza A virus macrophages polarization cyclosporine A cyclophilin A inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.861292/full |
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