CC chemokine receptors (or beta chemokine receptors) are integral membrane proteins that specifically bind and respond to cytokines of the CC chemokine family. They represent one subfamily of chemokine receptors, a large family of G protein-linked receptors that are known as seven transmembrane (7-TM) proteins since they span the cell membrane seven times. To date, ten true members of the CC chemokine receptor subfamily have been described. These are named CCR1 to CCR10 according to the IUIS/WHO Subcommittee on Chemokine Nomenclature.
CCR6, a receptor for CCL20, is expressed on unactivated memory T-cells and some dendritic cells. CCR6 is also expressed on Th17 cells.[14] CCR6 is down-regulated in activated T-cells.[15]
CCR7 is a highly important receptor with a role in trafficking of B and T lymphocytes and dendritic cells to and across high endothelial venules and positioning those cells correctly in T cell zones of secondary lymphoid organs. Its ligands include the related chemokines CCL19 and CCL21, (previously called ELC and SLC).[16]
CCR8 is associated with Th2 lymphocytes and is therefore found predominantly in the thymus (in humans) although some expression can be found in the brain, spleen, lymph node, and monocytes at the nucleotide level. The ligands for this receptor are CCL1 and CCL16[17]
CCR9 was previously called orphan receptor GPR 9-6 and is very highly expressed in thymus (on both immature and mature T-cells) while low in lymph nodes and spleen. CCR9 is also abundant in the gut, with its expression associated with T cells of the intestine. The specific ligand of this receptor is CCL25[18] To note, the chemokine binding protein D6 had previously been named CCR9, but this molecule is a scavenger receptor not a true (signaling) chemokine receptor.
CCR10 is receptor for CCL27 and CCL28 that was originally called orphan receptor GPR2.[8][19][20][21] CCR10 has been implicated in inflammation of the skin, and has been shown to recruit regulatory T cells (Tregs) to mucosal layers.
This molecule was originally designated CCR11 due to its ability to bind several CC chemokines (including CCL19, CCL21 and CCL25) and its structural similarity to chemokine receptors. However, due to the inability of this molecule (also known as CCRL1 and CCX CKR) to generate a signal following ligand interaction, it has been suggested that it is a scavenger receptor for chemokines and not a bona fide chemokine receptor. Thus CCRL1 should not be called CCR11 under the guidelines of the IUIS/WHO Subcommittee on Chemokine Nomenclature.
^ abYoun BS, Zhang SM, Lee EK, Park DH, Broxmeyer HE, Murphy PM, et al. (December 1997). "Molecular cloning of leukotactin-1: a novel human beta-chemokine, a chemoattractant for neutrophils, monocytes, and lymphocytes, and a potent agonist at CC chemokine receptors 1 and 3". Journal of Immunology. 159 (11): 5201–5. doi:10.4049/jimmunol.159.11.5201. PMID9548457. S2CID20622216.
^ abOgilvie P, Bardi G, Clark-Lewis I, Baggiolini M, Uguccioni M (April 2001). "Eotaxin is a natural antagonist for CCR2 and an agonist for CCR5". Blood. 97 (7): 1920–4. doi:10.1182/blood.v97.7.1920. PMID11264152.
^White JR, Imburgia C, Dul E, Appelbaum E, O'Donnell K, O'Shannessy DJ, et al. (November 1997). "Cloning and functional characterization of a novel human CC chemokine that binds to the CCR3 receptor and activates human eosinophils". Journal of Leukocyte Biology. 62 (5): 667–75. doi:10.1002/jlb.62.5.667. PMID9365122. S2CID12197497.
"Chemokine Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2016-03-03. Retrieved 2008-11-25.
