Chemokine-like receptor 1 (CMKLR1) and chemokine (C-C motif) receptor-like 2 (CCRL2); two multifunctional receptors with unusual properties.
Chemokine-like receptor 1 (CMKLR1) and chemokine (C-C motif) receptor-like 2 (CCRL2); two multifunctional receptors with unusual properties.
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DOI：
10.1016/j.yexcr.2010.10.023
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发表时间：
2011-03-10
影响因子：
3.7
通讯作者：
Oppenheim JJ
中科院分区：
文献类型：
--
作者：
Yoshimura T;Oppenheim JJ
趋化因子样受体 1 (CMKLR1)，也称为 ChemR23 和趋化因子（C-C 基序）受体样 2 (CCRL2) 是 7 次跨膜受体，基于其与已知 G 蛋白偶联受体的同源性，于 1990 年代末被克隆。它们以前是孤儿受体，没有任何已知的生物学作用；然而，最近的研究确定了这些受体的配体，并且它们的功能已开始被揭示。血浆蛋白衍生的趋化剂凯莫瑞是 CMKLR1 的配体，凯莫瑞激活 CMKLR1 可诱导体外巨噬细胞和树突状细胞 (DC) 的迁移，表明其具有促炎作用。然而，使用 CMKLR 缺陷小鼠的体内研究表明，该受体具有抗炎作用，可能是由于耐受性浆细胞样 DC 的募集所致。 Chemerin/CMKLR1 相互作用还促进脂肪生成和血管生成。解析 E1 的抗炎脂质介质是另一种 CMKLR1 配体，它抑制白细胞浸润和促炎基因表达。这些不同的结果表明 CMKLR1 是一种多功能受体。据报道，趋化因子 CCL5 和 CCL19 与 CCRL2 结合。与趋化因子受体 (DARC)、D6 和 CCX-CKR 的达菲抗原一样，CCRL2 不发出信号，但它会持续循环，可能降低 CCL5 和 CCL19 的局部浓度以及随后的免疫反应。令人惊讶的是，CMKLR1 的配体凯莫瑞也是 CCRL2 的配体。 CCRL2 结合凯莫林并增加局部凯莫林浓度，以有效地将其呈递给附近细胞上的 CMKLR1，从而提供 CCRL2 和 CMKLR1 之间的联系。尽管这些发现表明其具有抗炎作用，但最近一项使用 CCRL2 缺陷小鼠的研究表明其具有促炎作用。因此，CCRL2也可能是多功能的。需要使用 CMKLR1 或 CCRL2 缺陷小鼠进行进一步研究，以进一步确定这些受体在免疫反应和其他细胞过程中的作用。
Chemokine-like receptor 1 (CMKLR1), also known as ChemR23, and chemokine (C-C motif) receptor-like 2 (CCRL2) are 7-transmembrane receptors that were cloned in the late 1990’s based on their homology to known G-protein-coupled receptors. They were previously orphan receptors without any known biological roles; however, recent studies identified ligands for these receptors and their functions have begun to be unveiled. The plasma protein-derived chemoattractant chemerin is a ligand for CMKLR1 and activation of CMKLR1 with chemerin induces the migration of macrophages and dendritic cells (DCs) in vitro, suggesting a pro-inflammatory role. However, in vivo studies using CMKLR-deficient mice suggest an anti-inflammatory role for this receptor, possibly due to the recruitment of tolerogenic plasmacytoid DCs. Chemerin/CMKLR1 interaction also promotes adipogenesis and angiogenesis. The anti-inflammatory lipid mediator, resolving E1, is another CMKLR1 ligand and it inhibits leukocyte infiltration and proinflammatory gene expression. These divergent results suggest that CMKLR1 is a multifunctional receptor. The chemokine CCL5 and CCL19 are reported to bind to CCRL2. Like Duffy antigen for chemokine receptor (DARC), D6 and CCX-CKR, CCRL2 does not signal, but it constitutively recycles, potentially reducing local concentration of CCL5 and CCL19 and subsequent immune responses. Surprisingly, chemerin, a ligand for CMKLR1, is a ligand for CCRL2. CCRL2 binds chemerin and increases local chemerin concentration to efficiently present it to CMKLR1 on nearby cells, providing a link between CCRL2 and CMKLR1. Although these findings suggest an anti-inflammatory role, a recent study using CCRL2-deficient mice indicates a proinflammatory role; thus, CCRL2 may also be multifunctional. Further studies using CMKLR1- or CCRL2-deficient mice are needed to further define the role of these receptors in immune responses and other cellular processes.
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DOI：
10.1084/jem.20080129
发表时间：
2009-01-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Albanesi C;Scarponi C;Pallotta S;Daniele R;Bosisio D;Madonna S;Fortugno P;Gonzalvo-Feo S;Franssen JD;Parmentier M;De Pità O;Girolomoni G;Sozzani S
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影响因子：
2.8
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Yoshimura, T
DOI：
10.1006/bbrc.1997.7981
发表时间：
1998-02-04
影响因子：
3.1
作者：
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通讯作者：
Li, Y
影响因子：
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作者：
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