Chemokines (chemotactic cytokines) are a family of chemoattractant molecules. They attract leukocytes to areas of inflammation and lesions, and play a key role in leukocyte activation. Originally defined as host defense proteins, chemokines are now known to play a much broader biological role []. They have a wide range of effects in many different cell types beyond the immune system, including, for example, various cells of the central nervous system [], and endothelial cells, where they may act as either angiogenic or angiostatic factors [].The chemokine family is divided into four classes based on the number and spacing of their conserved cysteines: 2 Cys residues may be adjacent (the CC family); separated by an intervening residue (the CXC family); have only one of the first two Cys residues (C chemokines); or contain both cysteines, separated by three intervening residues (CX3C chemokines).Chemokines exert their effects by binding to rhodopsin-like G protein-coupled receptors on the surface of cells. Following interaction with their specific chemokine ligands, chemokine receptors trigger a flux in intracellular calcium ions, which cause a cellular response, including the onset of chemotaxis. There are over fifty distinct chemokines and least 18 human chemokine receptors []. Although the receptors bind only a single class of chemokines, they often bind several members of the same class with high affinity. Chemokine receptors are preferentially expressedon important functional subsets of dendritic cells, monocytes and lymphocytes, including Langerhans cells and T helper cells [, ]. Chemokines and their receptors can also be subclassified into homeostatic leukocyte homing molecules (CXCR4, CXCR5, CCR7, CCR9) versus inflammatory/inducible molecules (CXCR1, CXCR2, CXCR3, CCR1-6, CX3CR1).Chemokine XC receptor 1 (XCR1), which this entry represents is a receptor for lymphotactin []. Lymphotactin is the only known member of the C (or XC) chemokine family, and is produced by certain subsets of T cells and natural killer cells and is also chemotactic for these cell types []. XCR1 is strongly expressed in placenta and at lower levels in the spleen and thymus and detected only at very low levels in peripheral blood leukocytes []. Within these tissues, expression is restricted to CD8+ T cells and natural killer cells [, ]. Binding of lymphotactin to XCR1 stimulates calcium mobilisation and migration in a pertussis toxin-sensitive manner, indicating coupling of the receptor to Gi type proteins [, ]. The matching expression patterns of both lymphotactin and its receptor suggest a role for the chemokine in self-recruitment of leukocytes [].
The chemokine family is divided into four classes based on the number and spacing of their conserved cysteines: 2 Cys residues may be adjacent (the CC family), or separated by an intervening residue (the CXC family), or have only one of the first two Cys residues (C chemokines), or contain both cysteines separated by three intervening residues (CX3C chemokines).This entry includes beta-chemokines (CC chemokines), in addition to gamma (C chemokines) and delta-chemokines (CX3C chemokines). CC chemokines stimulate mainly monocytes, but also basophils, eosinophils, T-lymphocytes, and natural killer (NK) cells. C-C motif chemokine 2 (CCL2) stimulates chemotaxis of monocytes and several cellular events associated with chemotaxis. Two other chemokines structurally related to CCL2 are CCL8 (MCP-2) and CCL7 (MCP-3) [].The C chemokine subfamily is composed of two members, XC chemokine ligand 1 (XCL1), also known as lymphotactin or SCM-1 alpha, and XC chemokine ligand 2 (XCL2), also known as SCM-1 beta []. The cognate receptor for these chemokines is XCR1 []. The only CX3C chemokine identified to date is CX3C chemokine ligand 1 (CX3CL1), also known as fractalkine or neurotactin. With its unique CX3CR1 receptor [], it is involved in adherence to the endothelium of the inflammatory monocyte population [].
Chemokines (chemotactic cytokines) are a family of chemoattractant molecules. They attract leukocytes to areas of inflammation and lesions, and play a key role in leukocyte activation. Originally defined as host defense proteins, chemokines are now known to play a much broader biological role []. They have a wide range of effects in many different cell types beyond the immune system, including, for example, various cells of the central nervous system [], and endothelial cells, where they may act as either angiogenic or angiostatic factors [].The chemokine family is divided into four classes based on the number and spacing of their conserved cysteines: 2 Cys residues may be adjacent (the CC family); separated by an intervening residue (the CXC family); have only one of the first two Cys residues (C chemokines); or contain both cysteines, separated by three intervening residues (CX3C chemokines).Chemokines exert their effects by binding to rhodopsin-like G protein-coupled receptors on the surface of cells. Following interaction with their specific chemokine ligands, chemokine receptors trigger a flux in intracellular calcium ions, which cause a cellular response, including the onset of chemotaxis. There are over fifty distinct chemokines and least 18 human chemokine receptors []. Although the receptors bind only a single class of chemokines, they often bind several members of the same class with high affinity. Chemokine receptors are preferentially expressed on important functional subsets of dendritic cells, monocytes and lymphocytes, including Langerhans cells and T helpercells [, ]. Chemokines and their receptors can also be subclassified into homeostatic leukocyte homing molecules (CXCR4, CXCR5, CCR7, CCR9) versus inflammatory/inducible molecules (CXCR1, CXCR2, CXCR3, CCR1-6, CX3CR1).The C chemokine subfamily is composed of two members, XC chemokine ligand 1 (XCL1), also known as lymphotactin or SCM-1 alpha, and XC chemokine ligand 2 (XCL2), also known as SCM-1 beta []. The cognate receptor for these chemokines is XCR1 [].XCL1 is an inflammatory chemokine that produced by activated CD8+ T cells and natural killer cells. It is involved in the mediation of interactions between antigen-presenting dendritic cells and T-cells, and induction of CD8+ effector T-cell responses [, ]. It is also involved in the formation of self-tolerance mechanisms through the development of T regulatory cells within the thymus []. Less is known about its closely related paralogue XCL2, although the in vitro functional profiles are virtually identical []. Human XCL2 and XCL1 amino acid sequences differ at only two positions near the N terminus [].Viral XCL1 (vXCL1) exclusively binds to CD4(-) rat dendritic cells (DC), a subset of DC that express the corresponding chemokine receptor XCR1, a strategy to subvert cytotoxic immune responses [].
