Chemokine-like receptor 1 expression and Chemerin-directed chemotaxis distinguish plasmacytoid from myeloid dendritic cells in human blood
Chemokine-like receptor 1 expression and Chemerin-directed chemotaxis distinguish plasmacytoid from myeloid dendritic cells in human blood
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DOI：
10.4049/jimmunol.174.1.244
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发表时间：
2005-01-01
影响因子：
4.4
通讯作者：
Butcher, EC
中科院分区：
文献类型：
--
作者：
Zabel, BA;Silverio, AM;Butcher, EC
浆细胞样树突状细胞(PDC)是免疫反应的多功能细胞，分泌I型IFN，并分化为强大的免疫原性或耐受性AM。PDCs可以表达淋巴组织的黏附和趋化因子受体，但在组织炎症过程中也被未知的机制招募。我们使用一种新的针对蛇形趋化素样受体1(CMKLR1)的单抗来评估其在人类循环白细胞中的表达。我们发现CMKLR1在人类血液中的循环pDC中表达，而髓系树突状细胞(MDCs)以及淋巴细胞、单核细胞、中性粒细胞和嗜酸性粒细胞呈阴性。我们确定CMKLR1的主要血清激动剂为趋化蛋白，这是一种蛋白水解性的引诱剂，也是唯一已知的CMKLR1的配体，我们表明趋化蛋白在凝血过程中被激活，并在体外趋化试验中吸引PDC而不是MDC。我们的结论是，CMKLR1的表达和趋化蛋白介导的趋化作用将循环中的PDCs与MDCs区分开来，为它们在出血或炎性蛋白酶活性部位对免疫反应的不同贡献或调节提供了潜在的机制。这个
Plasmacytoid dendritic cells (pDCs) are versatile cells of the immune response, secreting type I IFNs and differentiating into potent immunogenic or tolerogenic AM. pDCs can express adhesion and chemokine receptors for lymphoid tissues, but are also recruited by unknown mechanisms during tissue inflammation. We use a novel mAb specific for serpentine chemokine-like receptor 1 (CMKLR1) to evaluate its expression by circulating leukocytes in humans. We show that CMKLR1 is expressed by circulating pDCs in human blood, whereas myeloid DCs (mDCs) as well as lymphocytes, monocytes, neutrophils, and eosinophils are negative. We identify a major serum agonist activity for CMKLR1 as chemerin, a proteolytically activated attractant and the sole known ligand for CMKLR1, and we show that chemerin is activated during blood coagulation and attracts pDC but not mDC in ex vivo chemotaxis assays. We conclude that CMKLR1 expression and chemerin-mediated chemotaxis distinguish circulating pDCs from mDCs, providing a potential mechanism for their differential contribution to or regulation of immune responses at sites of bleeding or inflammatory protease activity. The