Neutrophil breaching of the blood vessel pericyte layer during diapedesis requires mast cell-derived IL-17A.

Autor: Joulia R; William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.; NHLI, Imperial College London, London, UK., Guerrero-Fonseca IM; William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.; Department of Molecular Biomedicine, CINVESTAV-IPN, Mexico City, Mexico., Girbl T; William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.; Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany., Coates JA; William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK., Stein M; William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK., Vázquez-Martínez L; William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK., Lynam E; William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK., Whiteford J; William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK., Schnoor M; Department of Molecular Biomedicine, CINVESTAV-IPN, Mexico City, Mexico., Voehringer D; Department of Infection Biology, University Hospital Erlangen and Friedrich-Alexander University Erlangen-Nuremberg (FAU), Erlangen, 91054, Germany., Roers A; Institute for Immunology, Heidelberg University Hospital, Heidelberg, Germany., Nourshargh S; William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.; Centre for Inflammation and Therapeutic Innovation, Queen Mary University of London, London, EC1M 6BQ, UK., Voisin MB; William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK. m.b.voisin@qmul.ac.uk.; Centre for Inflammation and Therapeutic Innovation, Queen Mary University of London, London, EC1M 6BQ, UK. m.b.voisin@qmul.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Nov 17; Vol. 13 (1), pp. 7029. Date of Electronic Publication: 2022 Nov 17.
DOI: 10.1038/s41467-022-34695-7
Abstrakt: Neutrophil diapedesis is an immediate step following infections and injury and is driven by complex interactions between leukocytes and various components of the blood vessel wall. Here, we show that perivascular mast cells (MC) are key regulators of neutrophil behaviour within the sub-endothelial space of inflamed venules. Using confocal intravital microscopy, we observe directed abluminal neutrophil motility along pericyte processes towards perivascular MCs, a response that created neutrophil extravasation hotspots. Conversely, MC-deficiency and pharmacological or genetic blockade of IL-17A leads to impaired neutrophil sub-endothelial migration and breaching of the pericyte layer. Mechanistically, identifying MCs as a significant cellular source of IL-17A, we establish that MC-derived IL-17A regulates the enrichment of key effector molecules ICAM-1 and CXCL1 in nearby pericytes. Collectively, we identify a novel MC-IL-17A-pericyte axis as modulator of the final steps of neutrophil diapedesis, with potential translational implications for inflammatory disorders driven by increased neutrophil diapedesis.
(© 2022. The Author(s).)
Databáze: MEDLINE
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