Immunity
Volume 50, Issue 2, 19 February 2019, Pages 378-389.e5
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Article
Chemokine Receptor Redundancy and Specificity Are Context Dependent

https://doi.org/10.1016/j.immuni.2019.01.009Get rights and content
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Highlights

  • Mice deficient in CCR1, CCR2, CCR3, and CCR5 (iCCRs) develop normally

  • iCCRs redundantly establish resting tissue-resident myelomonocytic cell populations

  • CCR2 dominates in controlling monocyte recruitment in acute inflammation

  • iCCRs are not involved in neutrophil or lymphocyte recruitment in acute inflammation

Summary

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.

Keywords

chemokines
inflammation
monocytes
dendritic cells
receptors
mouse models

Cited by (0)

2

Present address: Wellcome Centre for Cell-Matrix Research, Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK

3

These authors contributed equally

4

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