CC chemokine receptors (or beta chemokine receptors) are

integral membrane protein An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All ''transmembrane proteins'' are IMPs, but not all IMPs are transmembrane proteins. IMPs comprise a sign ...

s that specifically bind and respond to

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in au ...

s of the

CC chemokine CC, cc, or C-C may refer to: Arts, entertainment, and media Fictional characters * C.C. (''Code Geass''), a character in the ''Code Geass'' anime series, pronounced "C-two" * C.C. Babcock, a character in the American sitcom ''The Nanny'' * Com ...

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.

Mechanism

The CC chemokine receptors all work by activating the

G protein G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their a ...

G_i.senselab
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Types

Overview table

CCR1

CCR1 was the first CC chemokine receptor identified and binds multiple inflammatory/inducible (see inducible gene) CC chemokines (including CCL4, CCL5,

CCL6 Chemokine (C-C motif) ligand 6 (CCL6) is a small cytokine belonging to the CC chemokine family that has only been identified in rodents. In mice, CCL6 is expressed in cells from neutrophil and macrophage lineages, and can be greatly induced under ...

CCL14 Chemokine (C-C motif) ligand 14 (CCL14) is a small cytokine belonging to the CC chemokine family. It is also commonly known as HCC-1. It is produced as a protein precursor that is processed to generate a mature active protein containing 74 amino ...

CCL15 Chemokine (C-C motif) ligand 15 (CCL15) is a small cytokine belonging to the CC chemokine family that is also known as leukotactin-1, MIP5 and HCC-2. CCL15 is expressed in liver, small intestine, colon, and in certain leukocytes and macrophages ...

CCL16 Chemokine (C-C motif) ligand 16 (CCL16) is a small cytokine belonging to the CC chemokine family that is known under several pseudonyms, including Liver-expressed chemokine (LEC) and Monotactin-1 (MTN-1). This chemokine is expressed by the l ...

and CCL23). In humans, this receptor can be found on

peripheral blood lymphocytes Peripheral blood lymphocytes (PBL) are mature lymphocytes that circulate in the blood, rather than localising to organs (such as the spleen or lymph nodes). They comprise T cells, NK cells and B cells B cells, also known as B lymphocytes, ...

and

monocytes Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also inf ...

. There is some suggestion that this chemokine receptor is restricted to memory T-cells within the

lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic a ...

pool. This receptor is also designated

cluster of differentiation The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophen ...

marker CD191.

CCR2

CCR2 can interact with CCL2, CCL8 and

and has been identified on the surface of

, activated memory T cells,

B cells B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted o ...

, and

basophils Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsible for inflammator ...

in humans, and also in

peritoneal The peritoneum is the serous membrane forming the lining of the abdominal cavity or coelom in amniotes and some invertebrates, such as annelids. It covers most of the intra-abdominal (or coelomic) organs, and is composed of a layer of mes ...

macrophages Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...

in mice. CCR2 is also designated CD192.

CCR3

CCR3 is a receptor for multiple inflammatory/inducible CC chemokines, including CCL11, CCL26, CCL7, CCL13,

CCL24 Chemokine (C-C motif) ligand 24 (CCL24) also known as myeloid progenitor inhibitory factor 2 (MPIF-2) or eosinophil chemotactic protein 2 (eotaxin-2) is a protein that in humans is encoded by the ''CCL24'' gene. This gene is located on human chro ...

and CCL5 that attract

eosinophils Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. A ...

, and CCL28 that attracts B and T

s to mucosal tissues. It is most highly expressed in both

and

, but can also be found in Th1 and

Th2 The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considere ...

cells and airway

epithelial cells Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellu ...

. Thus CCR3 plays a role in allergic reactions. CCR3 is also known as CD193.

CCR4

CCR4 is expressed on Th2 T lymphocytes and is up-regulated by

T cell receptor The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding ...

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

CCR5 is expressed on several cell types including peripheral blood-derived dendritic cells, CD34+

hematopoietic Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cell ...

progenitor In genealogy, the progenitor (rarer: primogenitor; german: Stammvater or ''Ahnherr'') is the – sometimes legendary – founder of a family, line of descent, clan or tribe, noble house, or ethnic group.. Ebenda''Ahnherr:''"Stammvater eines ...

cells and certain activated/memory Th1 lymphocytes. This receptor is well defined as a major coreceptor implicated in susceptibility to

HIV-1 The subtypes of HIV include two major types, HIV type 1 (HIV-1) and HIV type 2 (HIV-2). HIV-1 is related to viruses found in chimpanzees and gorillas living in western Africa, while HIV-2 viruses are related to viruses found in the sooty mangabey ...

infection and disease. This receptor has several CC chemokine ligands including CCL2, CCL3, CCL4, CCL5, CCL11, CCL13,

and

CCR6

CCR6, a receptor for

CCL20 Chemokine (C-C motif) ligand 20 (CCL20) or liver activation regulated chemokine (LARC) or Macrophage Inflammatory Protein-3 (MIP3A) is a small cytokine belonging to the CC chemokine family. It is strongly chemotactic for lymphocytes and weakly at ...

, 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

CCR7 C-C chemokine receptor type 7 is a protein that in humans is encoded by the ''CCR7'' gene. Two ligands have been identified for this receptor: the chemokines (C-C motif) ligand 19 (CCL19/ELC) and (C-C motif) ligand 21 (CCL21). CCR7 has also rece ...

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 The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system, and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphatic or lymphoid ...

. Its ligands include the related chemokines

CCL19 Chemokine (C-C motif) ligand 19 (CCL19) is a protein that in humans is encoded by the ''CCL19'' gene. This gene is one of several CC cytokine genes clustered on the p-arm of chromosome 9. Cytokines are a family of secreted proteins involved in i ...

and

CCL21 Chemokine (C-C motif) ligand 21 (CCL21) is a small cytokine belonging to the CC chemokine family. This chemokine is also known as 6Ckine (because it has six conserved cysteine residues instead of the four cysteines typical to chemokines), exodus- ...

, (previously called ELC and SLC).

CCR8

CCR8 is associated with Th2 lymphocytes and is therefore found predominantly in the

thymus The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, thymus cell lymphocytes or '' T cells'' mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders ...

(in humans) although some expression can be found in the brain,

spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .

lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...

, and monocytes at the

nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecu ...

level. The ligands for this receptor are CCL1 and

CCR9

CCR9 C-C chemokine receptor type 9 is a protein that in humans is encoded by the ''CCR9'' gene. CCR9 has also recently been designated CDw199 (cluster of differentiation The cluster of differentiation (also known as cluster of designation or classi ...

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 gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans an ...

. The specific ligand of this receptor is

CCL25 Chemokine (C-C motif) ligand 25 (CCL25) is a small cytokine belonging to the CC chemokine family that is also known as TECK (Thymus-Expressed Chemokine). CCL25 is believed to play a role in the development of T-cells. It is chemotactic for thymo ...

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

CCR10 C-C chemokine receptor type 10 is a protein that in humans is encoded by the ''CCR10'' gene. Function Chemokines are a group of small (approximately 8 to 14 kD), mostly basic, structurally related molecules that regulate cell trafficking of va ...

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 The regulatory T cells (Tregs or Treg cells), formerly known as suppressor T cells, are a subpopulation of T cells that modulate the immune system, maintain tolerance to self-antigens, and prevent autoimmune disease. Treg cells are immunosu ...

(

Tregs The regulatory T cells (Tregs or Treg cells), formerly known as suppressor T cells, are a subpopulation of T cells that modulate the immune system, maintain tolerance to self-antigens, and prevent autoimmune disease. Treg cells are immunosup ...

) to mucosal layers.

CCR11

This molecule was originally designated CCR11 due to its ability to bind several CC chemokines (including

and

) 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.

References

External links

* {{DEFAULTSORT:Cc Chemokine Receptors Chemokine receptors Cell biology