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)
|
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