Pathways & interactions
CC chemokine receptor 8 (IPR004068)
Short name: Chemokine_CCR8
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 [PMID: 11544102]. 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 [PMID: 9689100], and endothelial cells, where they may act as either angiogenic or angiostatic factors [PMID: 7592998].
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 [PMID: 10714678]. 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 helper cells [PMID: 10601351, PMID: 9500790]. 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).
CC chemokine receptors are a subfamily of the chemokine receptors that specifically bind and respond to cytokines of the CC chemokine family. There are currently ten members of the CC chemokine receptor subfamily, named CCR1 to 10. The receptors receptors are found in monocytes, lymphocytes, basophils and eosinophils.
This entry represents CC chemokine receptor 8 (CCR8), which it is expressed predominantly in lymphoid tissues [PMID: 10611408, PMID: 9521068] and has also been found in glomerular podocytes [PMID: 12055238] and human umbilical vein endothelial cells (HUVECs) [PMID: 14576057]. CCR8 is associated with Th2 lymphocytes, which are critical for allergy, and has a role in lymphocyte activation, migration, proliferation and differentiation and in allergic diseases [PMID: 11340325, PMID: 10419462, PMID: 9521068]. CCR8 binds to CCL1 (also known as I-309) [PMID: 9211859, PMID: 10540332] and to CCL16 (also known as liver expressed chemokine) [PMID: 10910894]. It also exhibits a high affinity for three chemokines of viral origin: vMIP-I, vMIP-II and vMCC-I.
GO:0016493 C-C chemokine receptor activity
GO:0016021 integral component of membrane