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 del Valle, Sandra D. Castillo, Heidi C.E. Welch, Oliver Soehnlein, Mariona Graupera, Fátima Sánchez-Cabo, Alexander Zarbock, Thomas E. Smithgall, Mauro Di Pilato, Thorsten R. MempelPierre Louis Tharaux, Santiago F. González, Angel Ayuso-Sacido, Lai Guan Ng, Gabriel F. Calvo, Iván González-Díaz, Fernando Díaz-de-María, Andrés Hidalgo

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)415-421
Number of pages7
JournalNature
Volume601
Issue number7893
DOIs
StatePublished - Jan 20 2022

ASJC Scopus subject areas

  • General

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