Behavioural immune landscapes of inflammation.

Autor: Crainiciuc G; Area of Cell and Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain., Palomino-Segura M; Area of Cell and Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain., Molina-Moreno M; Department of Signal Processing and Communication, Universidad Carlos III de Madrid, Madrid, Spain., Sicilia J; Area of Cell and Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.; Bioinformatics Unit, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain., Aragones DG; Department of Mathematics & MOLAB-Mathematical Oncology Laboratory, Universidad de Castilla-La Mancha, Ciudad Real, Spain., Li JLY; Area of Cell and Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.; Singapore Immunology Network (SIgN), A*STAR, Biopolis, Singapore., Madurga R; Faculty of Experimental Sciences and Faculty of Medicine, Universidad Francisco de Vitoria, Madrid, Spain., Adrover JM; Area of Cell and Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain., Aroca-Crevillén A; Area of Cell and Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain., Martin-Salamanca S; Area of Cell and Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain., Del Valle AS; Area of Cell and Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain., Castillo SD; Endothelial Pathobiology and Microenviroment Group, Josep Carreras Leukaemia Research Institute (IJC), 08916 Badalona, Barcelona, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain., Welch HCE; Signalling Programme, Babraham Institute, Cambridge, UK., Soehnlein O; Institute for Experimental Pathology, Center for Molecular Biology of Inflammation, Westfälische Wilhelms-Universität, Münster, Germany., Graupera M; Endothelial Pathobiology and Microenviroment Group, Josep Carreras Leukaemia Research Institute (IJC), 08916 Badalona, Barcelona, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain., Sánchez-Cabo F; Bioinformatics Unit, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain., Zarbock A; Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany., Smithgall TE; Department of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA., Di Pilato M; Center for Immunology and Inflammatory Diseases at Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.; Department of Immunology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Mempel TR; Center for Immunology and Inflammatory Diseases at Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Tharaux PL; Université de Paris, Paris Cardiovascular Center, Inserm, Paris, France., González SF; Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland., Ayuso-Sacido A; Faculty of Experimental Sciences and Faculty of Medicine, Universidad Francisco de Vitoria, Madrid, Spain.; Brain Tumor Laboratory, Fundación Vithas, Grupo Hospitales Vithas, Madrid, Spain., Ng LG; Singapore Immunology Network (SIgN), A*STAR, Biopolis, Singapore., Calvo GF; Department of Mathematics & MOLAB-Mathematical Oncology Laboratory, Universidad de Castilla-La Mancha, Ciudad Real, Spain., González-Díaz I; Department of Signal Processing and Communication, Universidad Carlos III de Madrid, Madrid, Spain., Díaz-de-María F; Department of Signal Processing and Communication, Universidad Carlos III de Madrid, Madrid, Spain., Hidalgo A; Area of Cell and Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain. ahidalgo@cnic.es.; Vascular Biology and Therapeutics Program and Department of Immunobiology, Yale University School of Medicine, New Haven, USA. ahidalgo@cnic.es.
Jazyk: angličtina
Zdroj: Nature [Nature] 2022 Jan; Vol. 601 (7893), pp. 415-421. Date of Electronic Publication: 2022 Jan 05.
DOI: 10.1038/s41586-021-04263-y
Abstrakt: Transcriptional and proteomic profiling of individual cells have revolutionized interpretation of biological phenomena by providing cellular landscapes of healthy and diseased tissues 1,2 . These approaches, however, do not describe dynamic scenarios in which cells continuously change their biochemical properties and downstream 'behavioural' outputs 3-5 . Here we used 4D live imaging to record tens to hundreds of morpho-kinetic parameters describing the dynamics of individual leukocytes at sites of active inflammation. By analysing more than 100,000 reconstructions of cell shapes and tracks over time, we obtained behavioural descriptors of individual cells and used these high-dimensional datasets to build behavioural landscapes. These landscapes recognized leukocyte identities in the inflamed skin and trachea, and uncovered a continuum of neutrophil states inside blood vessels, including a large, sessile state that was embraced by the underlying endothelium and associated with pathogenic inflammation. Behavioural screening in 24 mouse mutants identified the kinase Fgr as a driver of this pathogenic state, and interference with Fgr protected mice from inflammatory injury. Thus, behavioural landscapes report distinct properties of dynamic environments at high cellular resolution.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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