Behavioural immune landscapes of inflammation

Georgiana Crainiciuc, Miguel Palomino-Segura, Miguel Molina-Moreno, Jon Sicilia, David G. Aragones, Jackson Liang Yao Li, Rodrigo Madurga, José M. Adrover, Alejandra Aroca-Crevillén, Sandra Martin-Salamanca, Alfonso Serrano Valle, Sandra D. Castillo, Heidi C. E. Welch, Oliver Soehnlein, Mariona Graupera, Fátima Sánchez-Cabo, Alexander Zarbock, Thomas E. Smithgall, Mauro Pilato, Thorsten R. Mempel, Pierre-Louis Tharaux, Santiago F. González, Angel Ayuso-Sacido, Lai Guan Ng, Gabriel F. Calvo, Iván González-Díaz, Fernando Díaz- de-María and Andrés Hidalgo ()
Additional contact information
Georgiana Crainiciuc: Centro Nacional de Investigaciones Cardiovasculares Carlos III
Miguel Palomino-Segura: Centro Nacional de Investigaciones Cardiovasculares Carlos III
Miguel Molina-Moreno: Universidad Carlos III de Madrid
Jon Sicilia: Centro Nacional de Investigaciones Cardiovasculares Carlos III
David G. Aragones: Department of Mathematics & MOLAB-Mathematical Oncology Laboratory, Universidad de Castilla-La Mancha
Jackson Liang Yao Li: Centro Nacional de Investigaciones Cardiovasculares Carlos III
Rodrigo Madurga: Universidad Francisco de Vitoria
José M. Adrover: Centro Nacional de Investigaciones Cardiovasculares Carlos III
Alejandra Aroca-Crevillén: Centro Nacional de Investigaciones Cardiovasculares Carlos III
Sandra Martin-Salamanca: Centro Nacional de Investigaciones Cardiovasculares Carlos III
Alfonso Serrano Valle: Centro Nacional de Investigaciones Cardiovasculares Carlos III
Sandra D. Castillo: Endothelial Pathobiology and Microenviroment Group, Josep Carreras Leukaemia Research Institute (IJC), 08916 Badalona
Heidi C. E. Welch: Signalling Programme, Babraham Institute
Oliver Soehnlein: Institute for Experimental Pathology, Center for Molecular Biology of Inflammation, Westfälische Wilhelms-Universität
Mariona Graupera: Endothelial Pathobiology and Microenviroment Group, Josep Carreras Leukaemia Research Institute (IJC), 08916 Badalona
Fátima Sánchez-Cabo: Bioinformatics Unit, Centro Nacional de Investigaciones Cardiovasculares Carlos III
Alexander Zarbock: University Hospital Münster
Thomas E. Smithgall: University of Pittsburgh, School of Medicine
Mauro Pilato: Harvard Medical School
Thorsten R. Mempel: Harvard Medical School
Pierre-Louis Tharaux: Université de Paris, Paris Cardiovascular Center, Inserm
Santiago F. González: Università della Svizzera Italiana
Angel Ayuso-Sacido: Universidad Francisco de Vitoria
Lai Guan Ng: Singapore Immunology Network (SIgN), A*STAR
Gabriel F. Calvo: Department of Mathematics & MOLAB-Mathematical Oncology Laboratory, Universidad de Castilla-La Mancha
Iván González-Díaz: Universidad Carlos III de Madrid
Fernando Díaz- de-María: Universidad Carlos III de Madrid
Andrés Hidalgo: Centro Nacional de Investigaciones Cardiovasculares Carlos III

Nature, 2022, vol. 601, issue 7893, 415-421

Abstract: Abstract Transcriptional and proteomic profiling of individual cells have revolutionized interpretation of biological phenomena by providing cellular landscapes of healthy and diseased tissues1,2. These approaches, however, do not describe dynamic scenarios in which cells continuously change their biochemical properties and downstream ‘behavioural’ outputs3–5. 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.

Date: 2022
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DOI: 10.1038/s41586-021-04263-y

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