Article ; Online: Chemokine Receptor Redundancy and Specificity Are Context Dependent.
2019 Volume 50, Issue 2, Page(s) 378–389.e5
Abstract: 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 ... ...
Abstract | 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. |
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MeSH term(s) | Animals ; Chemokines/immunology ; Chemokines/metabolism ; Eosinophils/immunology ; Eosinophils/metabolism ; Gene Expression Profiling/methods ; Inflammation/genetics ; Inflammation/immunology ; Inflammation/metabolism ; Lymphocytes/immunology ; Lymphocytes/metabolism ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Monocytes/immunology ; Monocytes/metabolism ; Neutrophils/immunology ; Neutrophils/metabolism ; Receptors, CCR/genetics ; Receptors, CCR/immunology ; Receptors, CCR/metabolism ; Receptors, CCR1/immunology ; Receptors, CCR1/metabolism ; Receptors, CCR2/immunology ; Receptors, CCR2/metabolism ; Receptors, CCR3/immunology ; Receptors, CCR3/metabolism ; Receptors, CCR5/immunology ; Receptors, CCR5/metabolism |
Chemical Substances | CCR5 protein, mouse ; Ccr1 protein, mouse ; Ccr3 protein, mouse ; Chemokines ; Receptors, CCR ; Receptors, CCR1 ; Receptors, CCR2 ; Receptors, CCR3 ; Receptors, CCR5 |
Language | English |
Publishing date | 2019-02-19 |
Publishing country | United States |
Document type | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 1217235-2 |
ISSN | 1097-4180 ; 1074-7613 |
ISSN (online) | 1097-4180 |
ISSN | 1074-7613 |
DOI | 10.1016/j.immuni.2019.01.009 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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