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 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.
Authors
- Alberto Berral-González (ORCID: https://orcid.org/0000-0001-8388-6051)
- Jordi Alcaraz (ORCID: https://orcid.org/0000-0001-7898-1599)
- Julian Downward (ORCID: https://orcid.org/0000-0002-2331-4729)
- Ana Carreras‐González
- Esther Castellano (ORCID: https://orcid.org/0000-0002-8449-4081)
- Agata Krygowska
- Pedro R. Cutillas (ORCID: https://orcid.org/0000-0002-3426-2274)
- Vinothini Rajeeve (ORCID: https://orcid.org/0000-0002-6361-4291)
- Enrique Gabandé‐Rodríguez (ORCID: https://orcid.org/0000-0002-9715-8714)
- Mathieu-Benoı̂t Voisin
- María Carmen García-Macías (ORCID: https://orcid.org/0000-0002-5929-4926)
- Alejandro Rosell (ORCID: https://orcid.org/0000-0001-8028-8144)
- Héctor Sanz-Fraile (ORCID: https://orcid.org/0000-0003-2822-5108)
- Juan F. De Paz (ORCID: https://orcid.org/0000-0001-9461-7922)
- Juan Anguíta (ORCID: https://orcid.org/0000-0003-2061-7182)
- Ottilie Swinyard (ORCID: https://orcid.org/0000-0001-8474-8865)
- Javier De Las Rivas (ORCID: https://orcid.org/0000-0002-0984-9946)
- Cristina Cuesta (ORCID: https://orcid.org/0000-0002-5430-4611)
- Marta Alcón Pérez
Institutions
- Ikerbasque (ES)
- Consejo Superior de Investigaciones Científicas (ES)
- Queen Mary University of London (GB)
- Universidad de Salamanca (ES)
- The Francis Crick Institute (GB)
- CIC bioGUNE (ES)
- Barcelona Institute of Science and Technology (ES)
- Centro de Investigación del Cáncer (ES)
- Institute for Bioengineering of Catalonia (ES)
- William Harvey Research Institute (GB)
- Universitat de Barcelona (ES)
Publication Details
- Journal
- eLife
- Published
- 2025-04-24
- DOI
- https://doi.org/10.7554/elife.94590.4
- Citations
- 1
- Primary Topic
- Immune cells in cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.80
Funders
- Marie Curie
- Ministerio de Ciencia e Innovación
- Junta de Castilla y León
- Consejo Superior de Investigaciones Científicas
- Barts Cancer Institute