Immunity (Cambridge, Mass.), 2019-02, Vol.50 (2), p.378-389.e5
2019
Details
- Autor(en) / Beteiligte
- Titel
- Chemokine Receptor Redundancy and Specificity Are Context Dependent
- Ist Teil von
- Immunity (Cambridge, Mass.), 2019-02, Vol.50 (2), p.378-389.e5
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2019
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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. •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 CCR1, CCR2, CCR3, and CCR5 (iCCRs) are dominant regulators of myelomonocytic cell recruitment in inflammatory disease. Here, Dyer et al. have deleted the genomic locus incorporating the iCCRs in mice and demonstrate redundancy of iCCR involvement in establishing tissue-resident myelomonocytic cell populations yet specificity of iCCR use in acute inflammation.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1074-7613eISSN: 1097-4180DOI: 10.1016/j.immuni.2019.01.009Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6382461
- Format
- –
- Schlagworte
- Animal tissues, Animals, CC chemokine receptors, CCR1 protein, CCR2 protein, CCR5 protein, Chemokine receptors, Chemokines, Chemokines - immunology, Chemokines - metabolism, Chromosomes, Clonal deletion, Combinatorial analysis, dendritic cells, Eosinophils - immunology, Eosinophils - metabolism, Gene Expression Profiling - methods, Inflammation, Inflammation - genetics, Inflammation - immunology, Inflammation - metabolism, Leukocytes, Leukocytes (eosinophilic), Leukocytes (neutrophilic), Lymphocytes, Lymphocytes - immunology, Lymphocytes - metabolism, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Monocyte chemoattractant protein 1, Monocytes, Monocytes - immunology, Monocytes - metabolism, mouse models, Neutrophils - immunology, Neutrophils - metabolism, Receptors, 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, Redundancy, Rodents, Statistical analysis