The Chemokine Superfamily Revisited

Abstract

The chemokine superfamily consists of a large number of ligands and receptors. At first glance, this family appears redundant and their ligand-receptor relationships promiscuous, making its study challenging. However, analyzing this family from the evolutionary perspective greatly simplifies understanding both the organization and function of this apparently complex system. In particular, the functions of a subgroup of chemokines (designated homeostatic chemokines) have played pivotal roles in advancing our understanding of the organization and function of the cellular networks that shape the immune system. Here, we update the full scope of the human and mouse chemokine superfamilies, their relationships, and summarize several important roles that homeostatic chemokines play in the immune system.

Identification and expression analysis of an atypical chemokine receptor-2 (ACKR2)/CC chemokine binding protein-2 (CCBP2) in rainbow trout (Oncorhynchus mykiss)

“…The newly identified ACKR2 molecules showed top hits to ACKR2, and CCRL and CCR molecules clustered on human chromosome 3 [1,4,20], by BLAST search. Therefore, a neighbour-joining phylogenetic tree was constructed that included these CCR and CCRL molecules that clustered on human chromosome 3.…”

“…The coordinated movement of leucocytes is mediated primarily by the chemokine system that includes a large number of ligands binding to a smaller number of receptors [1e3]. For example, the human chemokine system consists of 48 ligands and 23 receptors [1,4]. The chemokine ligands have been classified into four groups (CC, CXC, CX3C, and XC) based on the position of the first two cysteine residues [5e7].…”

“…ACKRs serve homeostatic functions by clearing chemokines from the circulation and tissues [1,4,14e16]. ACKR1 binds a large number of CXC and CC inflammatory but not homeostatic chemokines, is abundantly expressed by erythrocytes, and functions as a chemokine sink [1,4]. Human ACKR2 binds at least 12 inflammatory CC chemokines and plays well characterized roles in the regulation of the in vivo inflammatory response [11,12].…”

Basic chemokine-derived glycosaminoglycan binding peptides exert antiviral properties against dengue virus serotype 2, herpes simplex virus-1 and respiratory syncytial virus

“…Chemokines can be divided into four groups based on the position of two conserved NH2-terminal cysteine residues. The CC chemokines have two adjacent cysteine residues, whereas in CXC and CX3C chemokines these residues are separated by one or three amino acids (X), respectively [43]. In the C chemokine subfamily only one of the two NH2-terminal cysteine residues is conserved.…”

CXCL1 Inhibits Airway Smooth Muscle Cell Migration through the Decoy Receptor Duffy Antigen Receptor for Chemokines

“…CXCL1 facilitates its signaling by binding to its putative receptor, the chemokine receptor CXCR2, although it also was found to bind to CXCR1, albeit with lower affinity (20). Chemokine receptors belong to class A rhodopsin-like, seven-transmembrane, or heptahelical, G protein-coupled receptors (GPCRs), which in general, favor coupling to the Gai protein subunit (21).…”