Analysis of combinatorial chemokine receptor expression dynamics using multi-receptor reporter mice
- University of Glasgow, United Kingdom
- University of Manchester, United Kingdom
- Shandong University, China
- Technische Universität Dresden, Germany
Abstract
Inflammatory chemokines and their receptors are central to the development of inflammatory/immune pathologies. The apparent complexity of this system, coupled with lack of appropriate in vivo models, has limited our understanding of how chemokines orchestrate inflammatory responses and has hampered attempts at targeting this system in inflammatory disease. Novel approaches are therefore needed to provide crucial biological, and therapeutic, insights into the chemokine-chemokine receptor family. Here, we report the generation of transgenic multi-chemokine receptor reporter mice in which spectrally-distinct fluorescent reporters mark expression of CCRs 1, 2, 3 and 5, key receptors for myeloid cell recruitment in inflammation. Analysis of these animals has allowed us to define, for the first time, individual and combinatorial receptor expression patterns on myeloid cells in resting and inflamed conditions. Our results demonstrate that chemokine receptor expression is highly specific, and more selective than previously anticipated.
Data availability
Data relating to this study are available on Dryad (https://doi.org/10.5061/dryad.3r2280gjs). Mouse lines generated in this study will be available, on request, from the corresponding author.
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Data for ELIfe paper entitled 'Analysis of combinatorial chemokine receptor expression dynamics using multi-receptor reporter mice.Dryad Digital Repository, doi:10.5061/dryad.3r2280gjs.
Article and author information
Author details
Adrian Francis Stewart
Funding
Wellcome Trust (217093/Z/19/Z)
- Laura Medina-Ruiz
- Robin Bartolini
- Douglas P Dyer
- Francesca Vidler
- Catherine E Hughes
- Fabian Schuette
- Marieke Pingen
- Gerard J Graham
Medical Research Council (MRV0109721)
- Samantha Love
- Marieke Pingen
- Alan James Hayes
- Gerard J Graham
Max-Planck-Institute for Cell Biology and Genetics (open access funding)
- Adrian Francis Stewart
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Florent Ginhoux, Agency for Science Technology and Research, Singapore
Ethics
Animal experimentation: All experiments were carried out under the auspices of a UK Home Office Project License and were approved by the local University of Glasgow Ethical Review Committee.
Version history
- Received: July 23, 2021
- Preprint posted: August 12, 2021 (view preprint)
- Accepted: May 23, 2022
- Accepted Manuscript published: June 14, 2022 (version 1)
- Version of Record published: June 24, 2022 (version 2)
Copyright
© 2022, Medina-Ruiz et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Analysis of combinatorial chemokine receptor expression dynamics using multi-receptor reporter mice
eLife 11:e72418.
https://doi.org/10.7554/eLife.72418
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