Pulmonary environmental cues drive group 2 innate lymphoid cell dynamics in mice and humans

Puttur, F. et al. (2019) Pulmonary environmental cues drive group 2 innate lymphoid cell dynamics in mice and humans. Science Immunology, 4(36), eaav7638. (doi: 10.1126/sciimmunol.aav7638) (PMID:31175176) (PMCID:PMC6744282)

[img]
Preview
Text
185827.pdf - Accepted Version

4MB

Abstract

Group 2 innate lymphoid cells (ILC2s) are enriched in mucosal tissues (e.g., lung) and respond to epithelial cell–derived cytokines initiating type 2 inflammation. During inflammation, ILC2 numbers are increased in the lung. However, the mechanisms controlling ILC2 trafficking and motility within inflamed lungs remain unclear and are crucial for understanding ILC2 function in pulmonary immunity. Using several approaches, including lung intravital microscopy, we demonstrate that pulmonary ILC2s are highly dynamic, exhibit amoeboid-like movement, and aggregate in the lung peribronchial and perivascular spaces. They express distinct chemokine receptors, including CCR8, and actively home to CCL8 deposits located around the airway epithelium. Within lung tissue, ILC2s were particularly motile in extracellular matrix–enriched regions. We show that collagen-I drives ILC2 to markedly change their morphology by remodeling their actin cytoskeleton to promote environmental exploration critical for regulating eosinophilic inflammation. Our study provides previously unappreciated insights into ILC2 migratory patterns during inflammation and highlights the importance of environmental guidance cues in the lung in controlling ILC2 dynamics.

Item Type:Articles
Additional Information:L.M.C. thanks the MRC (MR/M01245X/1) and Cancer Research UK for funding (Institute group funding ref 23983). This study was funded by the Wellcome Trust grant 107059/Z/15/Z, awarded to C.M.L. who is a Wellcome Senior Fellow in Basic Biomedical Sciences.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McGhee, Dr Ewan and Carlin, Dr Leo
Authors: Puttur, F., Denney, L., Gregory, L. G., Vuononvirta, J., Oliver, R., Entwistle, L. J., Walker, S. A., Headley, M. B., McGhee, E., Pease, J. E., Krummel, M. F., Carlin, L., and Lloyd, C. M.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Science Immunology
Publisher:American Association for the Advancement of Science
ISSN:2470-9468
ISSN (Online):2470-9468
Published Online:07 June 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Science Immunology 4(36):eaav7638
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

University Staff: Request a correction | Enlighten Editors: Update this record