CC chemokine receptors


CC 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 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.

Mechanism

The CC chemokine receptors all work by activating the G protein Gi.

Types

Overview table

CCR1

was the first CC chemokine receptor identified and binds multiple inflammatory/inducible CC chemokines. In humans, this receptor can be found on peripheral blood lymphocytes and monocytes. There is some suggestion that this chemokine receptor is restricted to memory T-cells within the lymphocyte pool. This receptor is also designated cluster of differentiation marker CD191.

CCR2

can interact with CCL2, CCL8 and CCL16 and has been identified on the surface of monocytes, activated memory T cells, B cells, and basophils in humans, and also in peritoneal macrophages in mice. CCR2 is also designated CD192.

CCR3

is a receptor for multiple inflammatory/inducible CC chemokines, including CCL11, CCL26, CCL7, CCL13, CCL15, CCL24 and CCL5 that attract eosinophils, and CCL28 that attracts B and T lymphocytes to mucosal tissues. It is most highly expressed in both eosinophils and basophils, but can also be found in Th1 and Th2 cells and airway epithelial cells. Thus CCR3 plays a role in allergic reactions. CCR3 is also known as CD193.

CCR4

is expressed on Th2 T lymphocytes and is up-regulated by T cell receptor activation. However, some reports suggest a role for this receptor also in trafficking of dendritic cells. The CC chemokines CCL3, CCL5, CCL17 and CCL22 signal through this receptor.

CCR5

is expressed on several cell types including peripheral blood-derived dendritic cells, CD34+ hematopoietic progenitor cells and certain activated/memory Th1 lymphocytes. This receptor is well defined as a major coreceptor implicated in susceptibility to HIV-1 infection and disease. This receptor has several CC chemokine ligands including CCL2, CCL3, CCL4, CCL5, CCL11, CCL13, CCL14 and CCL16.

CCR6

, a receptor for CCL20, is expressed on unactivated memory T-cells and some dendritic cells. CCR6 is also expressed on Th17 cells. CCR6 is down-regulated in activated T-cells.

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,.

CCR8

is associated with Th2 lymphocytes and is therefore found predominantly in the thymus 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

CCR9

was previously called orphan receptor GPR 9-6 and is very highly expressed in thymus 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 To note, the chemokine binding protein D6 had previously been named CCR9, but this molecule is a scavenger receptor not a true chemokine receptor.

CCR10

is receptor for CCL27 and CCL28 that was originally called orphan receptor GPR2. CCR10 has been implicated in inflammation of the skin, and has been shown to recruit regulatory T cells to mucosal layers.

CCR11

This molecule was originally designated CCR11 due to its ability to bind several CC chemokines and its structural similarity to chemokine receptors. However, due to the inability of this molecule 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.