Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TT, UK.
Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TT, UK.
Immunity. 2019 Feb 19;50(2):378-389.e5. doi: 10.1016/j.immuni.2019.01.009.
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，我们对于趋化因子受体在炎症过程中的个体和组合作用还缺乏了解。我们报告了关于 Ccr1、Ccr2、Ccr3 和 Ccr5 复合缺失的小鼠的研究，这些受体共同控制单核细胞和嗜酸性粒细胞向静止和炎症部位的募集。对这些小鼠和每个单独受体缺失的小鼠的静止组织的分析提供了明确的证据，证明这些受体在建立组织驻留的单核细胞群体中存在冗余作用。相比之下，对细胞募集到炎症部位的分析提供了受体用于特定白细胞亚型的特异性的证据，没有表明全面的冗余。我们没有发现这些受体中的任何一个在招募中性粒细胞或淋巴细胞到静止或急性炎症组织中的作用。我们的数据为组合炎症趋化因子受体功能提供了重要的启示，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。
