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

Medina-Ruiz, L. et al. (2022) Analysis of combinatorial chemokine receptor expression dynamics using multi-receptor reporter mice. eLife, 11, e72418. (doi: 10.7554/eLife.72418) (PMID:35699420) (PMCID:PMC9236609)

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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.

Item Type:Articles
Additional Information:Funding: Wellcome Trust (217093/Z/19/Z); Medical Research Council (MRV0109721); Max-Planck-Institute for Cell Biology and Genetics (open access funding); University of Glasgow.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Dyer, Dr Douglas and Schuette, Dr Fabian and Love, Samantha and Hughes, Dr Catherine and Vidler, Ms Francesca and Bartolini, Mr Robin and Medina-Ruiz, Dr Laura and Graham, Professor Gerard and Wilson, Dr Gillian
Creator Roles:
Medina-Ruiz, L.Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Supervision, Writing – original draft, Writing – review and editing
Bartolini, R.Conceptualization, Data curation, Formal analysis, Investigation, Supervision, Writing – original draft
Wilson, G.Formal analysis, Investigation, Methodology
Dyer, D.Conceptualization, Data curation, Formal analysis, Investigation, Supervision, Writing – original draft
Vidler, F.Data curation, Formal analysis, Investigation, Writing – original draft
Hughes, C.Data curation, Formal analysis, Project administration, Writing – original draft
Schuette, F.Conceptualization, Formal analysis, Investigation, Writing – original draft
Love, S.Data curation, Formal analysis, Investigation, Writing – original draft
Graham, G.Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Project administration, Supervision, Writing – original draft, Writing – review and editing
Authors: Medina-Ruiz, L., Bartolini, R., Wilson, G. J., Dyer, D. P., Vidler, F., Hughes, C. E., Schuette, F., Love, S., Fu, J., Stewart, A. F., and Graham, G. J.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:eLife
Publisher:eLife Sciences Publications
ISSN:2050-084X
ISSN (Online):2050-084X
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in eLife 11:e72418
Publisher Policy:Reproduced under a Creative Commons License
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
306649Defining chemokine receptor involvement in the myelomonocytic inflammatory responseGerard GrahamWellcome Trust (WELLCOTR)217093/Z/19/ZIII - Immunology