Japan residues, CXC and CC, depending on whether the first two cysteine residues have an amino acid between them Chemokines are a group of small (8–14 kDa), mostly(CXC) or are adjacent (CC). The genes for these families basic, structurally related molecules that regulate cell are currently designated SCY (small secreted cytokine) trafficking of various types of leukocytes through inter- with SCYa corresponding to the CC subfamily and SCYb actions with a subset of seven-transmembrane, G pro- to the CXC subfamily. Two other classes of chemokines tein–coupledreceptors. About40chemokineshavenow have been described: lymphotactin (C or SCYc) and been identified in humans. They mainly act on neutro- fractalkine (CX3C or SCYd). The former one lacks cystephils, monocytes, lymphocytes, and eosinophils and ines one and three of the typical chemokine structure play a pivotal role in host defense mechanisms. The(Kelner et al., 1994), while the latter one exhibits three study of chemokines has recently overlapped more with amino acids between the first two cysteines and is also other fields of immunology. It has now become evident the only membrane-bound chemokine through a mucinthat chemokines play fundamental roles in the develop- like stalk (Bazan et al., 1997). The proposed chemokine ment, homeostasis, and function of the immune system. nomenclature is based on the chemokine receptor no-The rapid increase in the number of chemokines along menclature currently in use, which uses CC, CXC, XC, with other complex issues described below have led to or CX3C followed by R (for receptor) and then a number. a situation where a newcomer attempting to understand Thus, we have CCR1–9, CXCR1–5, XCR1 (the lymphothis field faces a daunting task. In this review, our goal tactin receptor), and CX3CR1 (the fractalkine receptor). is to present a concise overview of the chemokine super- Basically, the new nomenclature replaces R with L (lifamily. The chemokines have a wide range of effects in gand instead of receptor) to designate the ligands and many different cell types beyond the immune system, uses CC for the SCYa family, CXC for SCYb, XC for including, for example, various cells of the central ner- SCYc, and CX3C for SCYd. The numbering system is vous system (Ma et al., 1998) or endothelial cells, where the one already in use to designate the genes encoding they result in either angiogenic or angiostatic effects each chemokine. Thus, a given gene will have the same (Strieter et al., 1995). However, the scope of this review number as its protein ligand (for example, ScyA 27 is makes it difficult to provide a comprehensive view of the gene encoding CCL27), a correlation that should such a complex and expanding field. For this reason, further simplify matters. Besides eliminating ambiguwe will focus on several areas of chemokine biology of ities, the new nomenclature directly indicates the class particular interest to immunologists. to which each chemokine belongs. The development of EST (expressed sequence tag) For many immunologists, it is important to know the databases and bioinformatics (computer-assisted se- mouse chemokines. The new nomenclature system, quence analysis) have allowed the rapid identification however, is currently focused on the human chemokines of novel genes. The chemokines have been particularly as “standard.” The chemokines described in other spewell suited for these techniques since they represent cies can be grouped into four categories.(1) Chemovery abundant messages in those cells that express kines that unambiguously (based on a high degree of them …