Tickets to the brain: Role of CCR2 and CX3CR1 in myeloid cell entry in the CNS
Tickets to the brain: Role of CCR2 and CX3CR1 in myeloid cell entry in the CNS
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DOI：
10.1016/j.jneuroim.2010.05.015
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发表时间：
2010-07-27
影响因子：
3.3
通讯作者：
Priller, Josef
中科院分区：
文献类型：
--
作者：
Prinz, Marco;Priller, Josef
在神经炎性和神经退行性疾病中，髓细胞是中枢神经系统(CNS)损伤和恢复的中介细胞。除了已经存在于大脑发育过程中的内源性骨髓单核细胞群体外，新迁移的白细胞被认为是成人大脑中重要的疾病调节器。因此，了解髓系细胞的募集对于控制免疫细胞进入中枢神经系统和潜在地减轻疾病负担至关重要。在髓系细胞植入脑内之前，它们首先系在激活的脑内皮细胞上并滚动，然后牢固地附着并最终迁移到受损的大脑中，在那里它们执行效应功能并分化为具有小胶质细胞样特征的细胞。这些步骤主要受黏附分子和趋化因子及其同源受体的调节。由于最近我们对单核细胞异质性的了解取得了进展，对趋化因子受体的兴趣显著增加。其中，趋化因子受体CCR2和CX3CR1的存在被认为对髓系细胞沿着发炎的血管运输和随后在大脑中积累都是至关重要的。因此，这些分子为中枢神经系统髓系细胞的治疗提供了可行的靶点。(C)2010爱思唯尔B.V.保留所有权利。
Myeloid cells are mediators of central nervous system (CNS) damage and recovery in neuroinflammatory and neurodegenerative disorders. Besides endogenous myelomonocytic cell populations that reside in the brain already during development, newly migrated leukocytes are considered as important disease modulators in the adult brain. Thus, understanding of myeloid cell recruitment is pivotal for manipulating immune cell entry into the CNS and potentially reducing disease burden. Before myeloid cells engraft in the brain, they first tether to and roll on the activated brain endothelium, then they firmly adhere and eventually transmigrate into the damaged brain where they execute effector functions and differentiate into cells with microglia-like features. These steps are mainly regulated by adhesion molecules and by chemokines and their cognate receptors. Due to recent advances in our understanding of monocyte heterogeneity, the interest in chemokine receptors has significantly increased. Among others, the presence of the chemokine receptors CCR2 and CX3CR1 is considered to be critical for both myeloid cell trafficking along inflamed vessels and subsequent accumulation in the brain. Therefore, these molecules present viable targets for therapeutic manipulations of myeloid cells destined for the CNS. (C) 2010 Elsevier B.V. All rights reserved.