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

  1. Laura Medina-Ruiz  Is a corresponding author
  2. Robin Bartolini
  3. Gillian J Wilson
  4. Douglas P Dyer
  5. Francesca Vidler
  6. Catherine E Hughes
  7. Fabian Schuette
  8. Samantha Love
  9. Marieke Pingen
  10. Alan James Hayes
  11. Jun Fu
  12. Adrian Francis Stewart
  13. Gerard J Graham  Is a corresponding author
  1. University of Glasgow, United Kingdom
  2. University of Manchester, United Kingdom
  3. Shandong University, China
  4. 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.

The following data sets were generated

Article and author information

Author details

  1. Laura Medina-Ruiz

    Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom
    For correspondence
    Laura.medina-ruiz@glasgow.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2934-534X
  2. Robin Bartolini

    Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Gillian J Wilson

    Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Douglas P Dyer

    Institute of Infection, Immunity and Inflammation, University of Manchester, Manchester, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Francesca Vidler

    Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Catherine E Hughes

    Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Fabian Schuette

    Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Samantha Love

    Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Marieke Pingen

    Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Alan James Hayes

    Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2708-6230
  11. Jun Fu

    Shandong University-HelmhoInstitute of Infection, Immunity and Inflammationof Biotechnology, Shandong University, Qingdao, China
    Competing interests
    The authors declare that no competing interests exist.
  12. Adrian Francis Stewart

    Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4754-1707
  13. Gerard J Graham

    Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom
    For correspondence
    gerard.graham@glasgow.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7801-204X

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

  1. 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

  1. Received: July 23, 2021
  2. Preprint posted: August 12, 2021 (view preprint)
  3. Accepted: May 23, 2022
  4. Accepted Manuscript published: June 14, 2022 (version 1)
  5. 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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  1. Laura Medina-Ruiz
  2. Robin Bartolini
  3. Gillian J Wilson
  4. Douglas P Dyer
  5. Francesca Vidler
  6. Catherine E Hughes
  7. Fabian Schuette
  8. Samantha Love
  9. Marieke Pingen
  10. Alan James Hayes
  11. Jun Fu
  12. Adrian Francis Stewart
  13. Gerard J Graham
(2022)
Analysis of combinatorial chemokine receptor expression dynamics using multi-receptor reporter mice
eLife 11:e72418.
https://doi.org/10.7554/eLife.72418

Share this article

https://doi.org/10.7554/eLife.72418

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