RAS–p110α signalling in macrophages is required for effective inflammatory response and resolution of inflammation
Macrophages are crucial in the body’s inflammatory response, with tightly regulated functions for optimal immune system performance. Our study reveals that the RAS–p110α signalling pathway, known for its involvement in various biological processes and tumourigenesis, regulates two vital aspects of t...
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eLife Sciences Publications Ltd
2025-04-01
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| Online Access: | https://elifesciences.org/articles/94590 |
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| author | Alejandro Rosell Agata Adelajda Krygowska Marta Alcón Pérez Cristina Cuesta Mathieu-Benoit Voisin Juan de Paz Héctor Sanz-Fraile Vinothini Rajeeve Ana Carreras-González Alberto Berral-González Ottilie Swinyard Enrique Gabandé-Rodríguez Julian Downward Jordi Alcaraz Juan Anguita Carmen García-Macías Javier De Las Rivas Pedro R Cutillas Esther Castellano Sanchez |
| author_facet | Alejandro Rosell Agata Adelajda Krygowska Marta Alcón Pérez Cristina Cuesta Mathieu-Benoit Voisin Juan de Paz Héctor Sanz-Fraile Vinothini Rajeeve Ana Carreras-González Alberto Berral-González Ottilie Swinyard Enrique Gabandé-Rodríguez Julian Downward Jordi Alcaraz Juan Anguita Carmen García-Macías Javier De Las Rivas Pedro R Cutillas Esther Castellano Sanchez |
| author_sort | Alejandro Rosell |
| collection | DOAJ |
| description | Macrophages are crucial in the body’s inflammatory response, with tightly regulated functions for optimal immune system performance. Our study reveals that the RAS–p110α signalling pathway, known for its involvement in various biological processes and tumourigenesis, regulates two vital aspects of the inflammatory response in macrophages: the initial monocyte movement and later-stage lysosomal function. Disrupting this pathway, either in a mouse model or through drug intervention, hampers the inflammatory response, leading to delayed resolution and the development of more severe acute inflammatory reactions in live models. This discovery uncovers a previously unknown role of the p110α isoform in immune regulation within macrophages, offering insight into the complex mechanisms governing their function during inflammation and opening new avenues for modulating inflammatory responses. |
| format | Article |
| id | doaj-art-d8fb19bb00894046ba90cd4e5abb90ff |
| institution | DOAJ |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-d8fb19bb00894046ba90cd4e5abb90ff2025-08-20T03:15:08ZengeLife Sciences Publications LtdeLife2050-084X2025-04-011310.7554/eLife.94590RAS–p110α signalling in macrophages is required for effective inflammatory response and resolution of inflammationAlejandro Rosell0Agata Adelajda Krygowska1Marta Alcón Pérez2Cristina Cuesta3Mathieu-Benoit Voisin4https://orcid.org/0000-0003-3001-0894Juan de Paz5Héctor Sanz-Fraile6Vinothini Rajeeve7https://orcid.org/0000-0002-6361-4291Ana Carreras-González8Alberto Berral-González9Ottilie Swinyard10Enrique Gabandé-Rodríguez11https://orcid.org/0000-0002-9715-8714Julian Downward12Jordi Alcaraz13Juan Anguita14Carmen García-Macías15Javier De Las Rivas16Pedro R Cutillas17https://orcid.org/0000-0002-3426-2274Esther Castellano Sanchez18https://orcid.org/0000-0002-8449-4081Tumour-Stroma Signalling Lab., Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, SpainCentre for Cancer and Inflammation, Barts Cancer Institute, Queen Mary University of London, London, United KingdomTumour-Stroma Signalling Lab., Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, SpainTumour-Stroma Signalling Lab., Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, SpainCentre for Microvascular Research, William Harvey Research Institute, Queen Mary University of London, London, United KingdomTumour-Stroma Signalling Lab., Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, SpainUnit of Biophysics and Bioengineering, Department of Biomedicine, School of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, SpainCentre for Cancer Genomics and Computational Biology, Cell Signalling and Proteomics Laboratory, Barts Cancer Institute, Queen Mary University of London, London, United KingdomBioinformatics and Functional Genomics, Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad de Salamanca, Salamanca, SpainInflammation and Macrophage Plasticity Lab, CIC bioGUNE, Derio, SpainCentre for Cancer and Inflammation, Barts Cancer Institute, Queen Mary University of London, London, United KingdomCentre for Cancer and Inflammation, Barts Cancer Institute, Queen Mary University of London, London, United KingdomOncogene Biology Laboratory, Francis Crick Institute, London, United KingdomUnit of Biophysics and Bioengineering, Department of Biomedicine, School of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain; Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute for Science and Technology (BIST), Barcelona, SpainInflammation and Macrophage Plasticity Lab, CIC bioGUNE, Derio, Spain; Ikerbasque, Basque Foundation for Science, Bilbao, Spain; Pathology Unit, Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer, Universidad de Salamanca, Salamanca, SpainPathology Unit, Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer, Universidad de Salamanca, Salamanca, SpainBioinformatics and Functional Genomics, Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad de Salamanca, Salamanca, SpainCentre for Cancer Genomics and Computational Biology, Cell Signalling and Proteomics Laboratory, Barts Cancer Institute, Queen Mary University of London, London, United KingdomTumour-Stroma Signalling Lab., Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain; Centre for Cancer and Inflammation, Barts Cancer Institute, Queen Mary University of London, London, United KingdomMacrophages are crucial in the body’s inflammatory response, with tightly regulated functions for optimal immune system performance. Our study reveals that the RAS–p110α signalling pathway, known for its involvement in various biological processes and tumourigenesis, regulates two vital aspects of the inflammatory response in macrophages: the initial monocyte movement and later-stage lysosomal function. Disrupting this pathway, either in a mouse model or through drug intervention, hampers the inflammatory response, leading to delayed resolution and the development of more severe acute inflammatory reactions in live models. This discovery uncovers a previously unknown role of the p110α isoform in immune regulation within macrophages, offering insight into the complex mechanisms governing their function during inflammation and opening new avenues for modulating inflammatory responses.https://elifesciences.org/articles/94590macrophagesinflammationRAS–p110α |
| spellingShingle | Alejandro Rosell Agata Adelajda Krygowska Marta Alcón Pérez Cristina Cuesta Mathieu-Benoit Voisin Juan de Paz Héctor Sanz-Fraile Vinothini Rajeeve Ana Carreras-González Alberto Berral-González Ottilie Swinyard Enrique Gabandé-Rodríguez Julian Downward Jordi Alcaraz Juan Anguita Carmen García-Macías Javier De Las Rivas Pedro R Cutillas Esther Castellano Sanchez RAS–p110α signalling in macrophages is required for effective inflammatory response and resolution of inflammation eLife macrophages inflammation RAS–p110α |
| title | RAS–p110α signalling in macrophages is required for effective inflammatory response and resolution of inflammation |
| title_full | RAS–p110α signalling in macrophages is required for effective inflammatory response and resolution of inflammation |
| title_fullStr | RAS–p110α signalling in macrophages is required for effective inflammatory response and resolution of inflammation |
| title_full_unstemmed | RAS–p110α signalling in macrophages is required for effective inflammatory response and resolution of inflammation |
| title_short | RAS–p110α signalling in macrophages is required for effective inflammatory response and resolution of inflammation |
| title_sort | ras p110α signalling in macrophages is required for effective inflammatory response and resolution of inflammation |
| topic | macrophages inflammation RAS–p110α |
| url | https://elifesciences.org/articles/94590 |
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