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.

目前，我们对趋化因子受体在炎症过程中的个体和组合作用缺乏了解。我们报告了对Ccr1 、 Ccr2 、 Ccr3和Ccr5复合缺失的小鼠的研究，这些缺失共同控制单核细胞和嗜酸性粒细胞向静止和发炎部位的募集。对这些小鼠和缺乏每种受体的小鼠的静息组织的分析，为这些受体在建立组织驻留单核细胞群中的冗余使用提供了明确的证据。相比之下，对发炎部位的细胞募集的分析提供了不同白细胞亚型受体使用特异性的证据，并且没有全面冗余的迹象。我们没有发现任何证据表明这些受体参与中性粒细胞或淋巴细胞向静息或急性发炎组织的募集。我们的数据为组合炎症趋化因子受体功能提供了重要线索，并强调Ccr2是急性炎症环境中骨髓单核细胞募集的主要驱动因素。