Myosin 1F Regulates M1-Polarization by Stimulating Intercellular Adhesion in Macrophages
Intestinal macrophages are highly mobile cells with extraordinary plasticity and actively contribute to cytokine-mediated epithelial cell damage. The mechanisms triggering macrophage polarization into a proinflammatory phenotype are unknown. Here, we report that during inflammation macrophages enhan...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.03118/full |
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| author | Zayda L. Piedra-Quintero Carolina Serrano Nicolás Villegas-Sepúlveda José L. Maravillas-Montero Sandra Romero-Ramírez Mineko Shibayama Oscar Medina-Contreras Porfirio Nava Leopoldo Santos-Argumedo |
| author_facet | Zayda L. Piedra-Quintero Carolina Serrano Nicolás Villegas-Sepúlveda José L. Maravillas-Montero Sandra Romero-Ramírez Mineko Shibayama Oscar Medina-Contreras Porfirio Nava Leopoldo Santos-Argumedo |
| author_sort | Zayda L. Piedra-Quintero |
| collection | DOAJ |
| description | Intestinal macrophages are highly mobile cells with extraordinary plasticity and actively contribute to cytokine-mediated epithelial cell damage. The mechanisms triggering macrophage polarization into a proinflammatory phenotype are unknown. Here, we report that during inflammation macrophages enhance its intercellular adhesion properties in order to acquire a M1-phenotype. Using in vitro and in vivo models we demonstrate that intercellular adhesion is mediated by integrin-αVβ3 and relies in the presence of the unconventional class I myosin 1F (Myo1F). Intercellular adhesion mediated by αVβ3 stimulates M1-like phenotype in macrophages through hyperactivation of STAT1 and STAT3 downstream of ILK/Akt/mTOR signaling. Inhibition of integrin-αVβ3, Akt/mTOR, or lack of Myo1F attenuated the commitment of macrophages into a pro-inflammatory phenotype. In a model of colitis, Myo1F deficiency strongly reduces the secretion of proinflammatory cytokines, decreases epithelial damage, ameliorates disease activity, and enhances tissue repair. Together our findings uncover an unknown role for Myo1F as part of the machinery that regulates intercellular adhesion and polarization in macrophages. |
| first_indexed | 2024-12-24T13:00:59Z |
| format | Article |
| id | doaj.art-53984ed54b9949d3820f639513674efb |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-24T13:00:59Z |
| publishDate | 2019-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-53984ed54b9949d3820f639513674efb2022-12-21T16:54:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-01-01910.3389/fimmu.2018.03118420600Myosin 1F Regulates M1-Polarization by Stimulating Intercellular Adhesion in MacrophagesZayda L. Piedra-Quintero0Carolina Serrano1Nicolás Villegas-Sepúlveda2José L. Maravillas-Montero3Sandra Romero-Ramírez4Mineko Shibayama5Oscar Medina-Contreras6Porfirio Nava7Leopoldo Santos-Argumedo8Department of Molecular Biomedicine, Cinvestav Zacatenco, Mexico City, MexicoDepartment of Physiology, Biophysics and Neurosciences, Cinvestav Zacatenco, Mexico City, MexicoDepartment of Molecular Biomedicine, Cinvestav Zacatenco, Mexico City, MexicoResearch Support Network, Universidad Nacional Autónoma de México and Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”, Mexico City, MexicoResearch Support Network, Universidad Nacional Autónoma de México and Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”, Mexico City, MexicoDepartment of Infectomics and Molecular Pathogenesis, Cinvestav Zacatenco, Mexico City, MexicoImmunology and Proteomics Laboratory, Mexico Children's Hospital Federico Gómez, Mexico City, MexicoDepartment of Physiology, Biophysics and Neurosciences, Cinvestav Zacatenco, Mexico City, MexicoDepartment of Molecular Biomedicine, Cinvestav Zacatenco, Mexico City, MexicoIntestinal macrophages are highly mobile cells with extraordinary plasticity and actively contribute to cytokine-mediated epithelial cell damage. The mechanisms triggering macrophage polarization into a proinflammatory phenotype are unknown. Here, we report that during inflammation macrophages enhance its intercellular adhesion properties in order to acquire a M1-phenotype. Using in vitro and in vivo models we demonstrate that intercellular adhesion is mediated by integrin-αVβ3 and relies in the presence of the unconventional class I myosin 1F (Myo1F). Intercellular adhesion mediated by αVβ3 stimulates M1-like phenotype in macrophages through hyperactivation of STAT1 and STAT3 downstream of ILK/Akt/mTOR signaling. Inhibition of integrin-αVβ3, Akt/mTOR, or lack of Myo1F attenuated the commitment of macrophages into a pro-inflammatory phenotype. In a model of colitis, Myo1F deficiency strongly reduces the secretion of proinflammatory cytokines, decreases epithelial damage, ameliorates disease activity, and enhances tissue repair. Together our findings uncover an unknown role for Myo1F as part of the machinery that regulates intercellular adhesion and polarization in macrophages.https://www.frontiersin.org/article/10.3389/fimmu.2018.03118/fullmyosin 1Fintercellular adhesionM1-polarizationinflammationAkt/mTOR/STAT signaling |
| spellingShingle | Zayda L. Piedra-Quintero Carolina Serrano Nicolás Villegas-Sepúlveda José L. Maravillas-Montero Sandra Romero-Ramírez Mineko Shibayama Oscar Medina-Contreras Porfirio Nava Leopoldo Santos-Argumedo Myosin 1F Regulates M1-Polarization by Stimulating Intercellular Adhesion in Macrophages Frontiers in Immunology myosin 1F intercellular adhesion M1-polarization inflammation Akt/mTOR/STAT signaling |
| title | Myosin 1F Regulates M1-Polarization by Stimulating Intercellular Adhesion in Macrophages |
| title_full | Myosin 1F Regulates M1-Polarization by Stimulating Intercellular Adhesion in Macrophages |
| title_fullStr | Myosin 1F Regulates M1-Polarization by Stimulating Intercellular Adhesion in Macrophages |
| title_full_unstemmed | Myosin 1F Regulates M1-Polarization by Stimulating Intercellular Adhesion in Macrophages |
| title_short | Myosin 1F Regulates M1-Polarization by Stimulating Intercellular Adhesion in Macrophages |
| title_sort | myosin 1f regulates m1 polarization by stimulating intercellular adhesion in macrophages |
| topic | myosin 1F intercellular adhesion M1-polarization inflammation Akt/mTOR/STAT signaling |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.03118/full |
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