Chemokine receptor redundancy and specificity are context dependent

Dyer, D. P. et al. (2019) Chemokine receptor redundancy and specificity are context dependent. Immunity, 50(2), 378-389.e5. (doi: 10.1016/j.immuni.2019.01.009) (PMID:30784579) (PMCID:PMC6382461)

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Currently, we lack an understanding of the individual and combinatorial roles for chemokine receptors in the inflammatory process. We report studies on mice with a compound deletion of Ccr1, Ccr2, Ccr3, and Ccr5, which together control monocytic and eosinophilic recruitment to resting and inflamed sites. Analysis of resting tissues from these mice, and mice deficient in each individual receptor, provides clear evidence for redundant use of these receptors in establishing tissue-resident monocytic cell populations. In contrast, analysis of cellular recruitment to inflamed sites provides evidence of specificity of receptor use for distinct leukocyte subtypes and no indication of comprehensive redundancy. We find no evidence of involvement of any of these receptors in the recruitment of neutrophils or lymphocytes to resting or acutely inflamed tissues. Our data shed important light on combinatorial inflammatory chemokine receptor function and highlight Ccr2 as the primary driver of myelomonocytic cell recruitment in acutely inflamed contexts.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Kelly, Dr Christopher and Pallas, Mr Kenny and Vidler, Francesca and Lee, Miss Kit and Hansell, Dr Chris and Hughes, Dr Catherine and Macleod, Dr Megan and Dyer, Dr Douglas and Schuette, Dr Fabian and Bartolini, Mr Robin and Medina-Ruiz, Dr Laura and Graham, Professor Gerard
Authors: Dyer, D. P., Medina-Ruiz, L., Bartolini, R., Schuette, F., Hughes, C. E., Pallas, K., Vidler, F., Macleod, M. K.L., Kelly, C. J., Lee, K. M., Hansell, C. A.H., and Graham, G. J.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Research Centre:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
Journal Name:Immunity
Publisher:Elsevier (Cell Press)
ISSN (Online):1097-4180
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Immunity 50(2): 378-389.e5
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
600961Dissecting the chemokine basis for the orchestration of the in vivo inflammatory responseGerard GrahamWellcome Trust (WELLCOTR)099251/Z/12/ZIII -IMMUNOLOGY
681091The ACKR2-CCR2 axis in development and diseaseGerard GrahamMedical Research Council (MRC)MR/M019764/1III -IMMUNOLOGY