Joulia Lab

Visualising the Lung Immune Response

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


Journal article


R. Joulia, I. M. Guerrero-Fonseca, Tamara Girbl, J. A. Coates, Monja Stein, Laura Vázquez-Martínez, Eleanor Lynam, J. Whiteford, M. Schnoor, D. Voehringer, Axel Roers, S. Nourshargh, M. Voisin
Nature Communications, 2022

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APA   Click to copy
Joulia, R., Guerrero-Fonseca, I. M., Girbl, T., Coates, J. A., Stein, M., Vázquez-Martínez, L., … Voisin, M. (2022). Neutrophil breaching of the blood vessel pericyte layer during diapedesis requires mast cell-derived IL-17A. Nature Communications.


Chicago/Turabian   Click to copy
Joulia, R., I. M. Guerrero-Fonseca, Tamara Girbl, J. A. Coates, Monja Stein, Laura Vázquez-Martínez, Eleanor Lynam, et al. “Neutrophil Breaching of the Blood Vessel Pericyte Layer during Diapedesis Requires Mast Cell-Derived IL-17A.” Nature Communications (2022).


MLA   Click to copy
Joulia, R., et al. “Neutrophil Breaching of the Blood Vessel Pericyte Layer during Diapedesis Requires Mast Cell-Derived IL-17A.” Nature Communications, 2022.


BibTeX   Click to copy

@article{r2022a,
  title = {Neutrophil breaching of the blood vessel pericyte layer during diapedesis requires mast cell-derived IL-17A},
  year = {2022},
  journal = {Nature Communications},
  author = {Joulia, R. and Guerrero-Fonseca, I. M. and Girbl, Tamara and Coates, J. A. and Stein, Monja and Vázquez-Martínez, Laura and Lynam, Eleanor and Whiteford, J. and Schnoor, M. and Voehringer, D. and Roers, Axel and Nourshargh, S. and Voisin, M.}
}

Abstract

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. The blood vessel wall is a complex multi-layered structure, yet upon injury or infection, neutrophil leukocytes are rapidly migrating from the blood stream to the affected tissues, by a process termed diapedesis. Authors here show that the final steps of diapedesis through the outer pericyte layer is regulated by perivascular mast cells via IL-17A production.