Yoshie O, Imai T, Nomiyama H
Department of Microbiology, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
Adv Immunol. 2001;78:57-110. doi: 10.1016/s0065-2776(01)78002-9.
Chemokines are a superfamily of small, heparin-binding cytokines that induce directed migration of various types of leukocytes through interactions with a group of seven-transmembrane G protein-coupled receptors. At present, over 40 members have been identified in humans. Until a few years ago, chemokines were mainly known as potent attractants for leukocytes such as neutrophils and monocytes, and were thus mostly regarded as the mediators of acute and chronic inflammatory responses. They had highly complex ligand-receptor relationships and their genes were regularly mapped on chromosomes 4 and 17 in humans. Recently, novel chemokines have been identified in rapid succession, mostly through application of bioinformatics on expressed sequence tag databases. A number of surprises have followed the identification of novel chemokines. They are constitutively expressed in lymphoid and other tissues with individually characteristic patterns. Most of them turned out to be highly specific for lymphocytes and dendritic cells. They have much simpler ligand-receptor relationships, and their genes are mapped to chromosomal loci different from the traditional chemokine gene clusters. Thus, the emerging chemokines are functionally and genetically quite different from the classical "inflammatory chemokines" and may be classified as "immune (system) chemokines" because of their profound importance in the genesis, homeostasis and function of the immune system. The emergence of immune chemokines has brought about a great deal of impact on the current immunological research, leading us to a better understanding on the fine traffic regulation of lymphocytes and dendritic cells. The immune chemokines and their receptors are also likely to be important future targets for therapeutic intervention of our immune responses.
趋化因子是一类小的、肝素结合细胞因子的超家族,它们通过与一组七跨膜G蛋白偶联受体相互作用,诱导各类白细胞的定向迁移。目前,已在人类中鉴定出40多个成员。直到几年前,趋化因子主要被认为是中性粒细胞和单核细胞等白细胞的强效吸引剂,因此大多被视为急性和慢性炎症反应的介质。它们具有高度复杂的配体 - 受体关系,其基因通常定位于人类染色体4和17上。最近,主要通过对表达序列标签数据库应用生物信息学,相继鉴定出了新型趋化因子。新型趋化因子的鉴定带来了许多惊喜。它们在淋巴组织和其他组织中组成性表达,具有各自独特的模式。其中大多数被证明对淋巴细胞和树突状细胞具有高度特异性。它们具有更简单的配体 - 受体关系,并且其基因定位于与传统趋化因子基因簇不同的染色体位点。因此,新出现的趋化因子在功能和遗传上与经典的“炎症趋化因子”有很大不同,由于它们在免疫系统的发生、稳态和功能中具有重要意义,可能被归类为“免疫(系统)趋化因子”。免疫趋化因子的出现对当前的免疫学研究产生了很大影响,使我们对淋巴细胞和树突状细胞的精细迁移调节有了更好的理解。免疫趋化因子及其受体也可能是未来免疫反应治疗干预的重要靶点。