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Analysis of combinatorial chemokine receptor expression dynamics using multi-receptor reporter mice

View ORCID ProfileLaura Medina-Ruiz, Robin Bartolini, Douglas P Dyer, Francesca Vidler, Catherine E Hughes, Fabian Schuette, Samantha Love, Jun Fu, View ORCID ProfileA. Francis Stewart, View ORCID ProfileGerard J Graham
doi: https://doi.org/10.1101/2021.08.11.455927
Laura Medina-Ruiz
1Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, 120 University Place, Glasgow G12 8TA, United Kingdom
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  • ORCID record for Laura Medina-Ruiz
  • For correspondence: Laura.Medina-Ruiz@glasgow.ac.uk gerard.graham@glasgow.ac.uk
Robin Bartolini
1Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, 120 University Place, Glasgow G12 8TA, United Kingdom
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Douglas P Dyer
1Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, 120 University Place, Glasgow G12 8TA, United Kingdom
2Wellcome Centre for Cell-Matrix Research and Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK
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Francesca Vidler
1Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, 120 University Place, Glasgow G12 8TA, United Kingdom
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Catherine E Hughes
1Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, 120 University Place, Glasgow G12 8TA, United Kingdom
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Fabian Schuette
1Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, 120 University Place, Glasgow G12 8TA, United Kingdom
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Samantha Love
1Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, 120 University Place, Glasgow G12 8TA, United Kingdom
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Jun Fu
3Center for Molecular and Cellular Bioengineering, Biotechnology Center, Technische Universität Dresden, 01307 Dresden, Germany
4Shandong University–Helmholtz Institute of Biotechnology, State Key Laboratory of Microbial Technology, School of Life Science, Shandong University, People’s Republic of China
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A. Francis Stewart
3Center for Molecular and Cellular Bioengineering, Biotechnology Center, Technische Universität Dresden, 01307 Dresden, Germany
5Max-Planck-Institute for Cell Biology and Genetics, 01307 Dresden, Germany
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Gerard J Graham
1Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, 120 University Place, Glasgow G12 8TA, United Kingdom
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  • For correspondence: Laura.Medina-Ruiz@glasgow.ac.uk gerard.graham@glasgow.ac.uk
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Summary

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.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted August 12, 2021.
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Analysis of combinatorial chemokine receptor expression dynamics using multi-receptor reporter mice
Laura Medina-Ruiz, Robin Bartolini, Douglas P Dyer, Francesca Vidler, Catherine E Hughes, Fabian Schuette, Samantha Love, Jun Fu, A. Francis Stewart, Gerard J Graham
bioRxiv 2021.08.11.455927; doi: https://doi.org/10.1101/2021.08.11.455927
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Analysis of combinatorial chemokine receptor expression dynamics using multi-receptor reporter mice
Laura Medina-Ruiz, Robin Bartolini, Douglas P Dyer, Francesca Vidler, Catherine E Hughes, Fabian Schuette, Samantha Love, Jun Fu, A. Francis Stewart, Gerard J Graham
bioRxiv 2021.08.11.455927; doi: https://doi.org/10.1101/2021.08.11.455927

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