The "C" sub-family of chemokine receptors contains only one member: XCR1, the receptor for XCL1 and XCL2 (or lymphotactin-1 and -2).
Contents
XCR1 is also known as GPR5.
The "C" sub-family of chemokine receptors contains only one member: XCR1, the receptor for XCL1 and XCL2 (or lymphotactin-1 and -2).
XCR1 is also known as GPR5.
The protein encoded by this gene is a chemokine receptor belonging to the G protein-coupled receptor superfamily. The family members are characterized by the presence of 7 transmembrane domains and numerous conserved amino acids. This receptor is most closely related to RBS11 and the MIP1-alpha/RANTES receptor. It transduces a signal by increasing the intracellular calcium ions level. The viral macrophage inflammatory protein-II is an antagonist of this receptor and blocks signaling. Two alternatively spliced transcript variants encoding the same protein have been found for this gene. [5]
Cross-presenting dendritic cells (DCs) in the spleen develop into XCR1+ DCs in the small intestine, T cell zones of Peyer's patches, and T cell zones and sinuses of mesenteric lymph nodes. XCR1+ DCs specialize in cross-presentations of orally applied antigens. The integrin SIRPα is also a differentiating factor for the XCR1+ DCs. The development transcription factor Batf3 helps develop the differences between XCR1+ DCs and CD103+ CD11b- DCs. [6]
XCL1 contributes to chemotaxis only in CD8+ murine cells, but not other DC types, B cells, T cells, or NK cells. Only some of these CD8+ murine cells expressed XCR1 receptors. NK cells release XCL1 along with IFN-γ and some other chemokines upon encountering certain bacteria such as Listeria or MCMV. XCR1+ and CD8+cells work together to cross-present antigen and communicate CD8+ activation. Cross presentation of XCR1+ CD8+ and XCR1+ CD8- cells was strongest, as is expected since they have XCR1 receptors. CD4+ and CD8+ may become outdated terms, since the activity of the cell appears to be primarily dependent upon the expression of XCR1, which will make a population far more similar than the expression of CD4 or CD8. [7]
XCR1+ cells are dependent on the growth factor Ftl3 ligand and are nonexistent in Batf3- deficient mice. Also, XCR1+ DCs are related to CD103+CD11b- DCs. [6]
XCL1 is expressed by medullary thymic epithelial T cells (mTECs) while XCR1 is expressed by thymic dendritic cells (tDCs). This communication helps with the destruction of cells that are not self-tolerant. When mice lose the ability to express XCL1, they are deficient in accumulation of tDCs and producing naturally occurring regulatory T cells (nT reg cells). The displaying of XCL1 by mTECs, tDC chemotaxis, and nT reg cell production are all decreased in mice that lack Aire, demonstrating it as an important regulator of XCL1 production. [8]
Naive CD8+ T cells are prepared when tumors form by cross-presentation via XCR1+ DCs and as a result will require a lower threshold to respond to antigen. Memory CD8+ T lymphocytes (mCTLs) are activated first after infection and then are signaled by CXCR3, IL-12, and CXCL9 by other XCR1+ DCs. In order to make a powerful secondary infection response, cytokine and chemokine signaling between XCR1+ DCs and NK cells must occur. [9]
Chemokines, or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In addition to playing a major role in the activation of host immune responses, chemokines are important for biological processes, including morphogenesis and wound healing, as well as in the pathogenesis of diseases like cancers.
Macrophage Inflammatory Proteins (MIP) belong to the family of chemotactic cytokines known as chemokines. In humans, there are two major forms, MIP-1α and MIP-1β that are now officially named CCL3 and CCL4, respectively. However, other names can sometimes be encountered, especially in older literature, as LD78α, AT 464.1 and GOS19-1 for human CCL3 and AT 744, Act-2, LAG-1, HC21 and G-26 for human CCL4. Other macrophage inflammatory proteins include MIP-2, MIP-3 and MIP-5.
Chemokine ligands 4 previously known as macrophage inflammatory protein (MIP-1β), is a protein which in humans is encoded by the CCL4 gene. CCL4 belongs to a cluster of genes located on 17q11-q21 of the chromosomal region. Identification and localization of the gene on the chromosome 17 was in 1990 although the discovery of MIP-1 was initiated in 1988 with the purification of a protein doublet corresponding to inflammatory activity from supernatant of endotoxin-stimulated murine macrophages. At that time, it was also named as "macrophage inflammatory protein-1" (MIP-1) due to its inflammatory properties.
Chemokine ligand 1 (CCL1) is also known as small inducible cytokine A1 and I-309 in humans. CCL1 is a small glycoprotein that belongs to the CC chemokine family.
Chemokine ligand 7 (CCL7) is a small cytokine that was previously called monocyte-chemotactic protein 3 (MCP3). CCL7 is a small protein that belongs to the CC chemokine family and is most closely related to CCL2.
Chemokine 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 attracts neutrophils. CCL20 is implicated in the formation and function of mucosal lymphoid tissues via chemoattraction of lymphocytes and dendritic cells towards the epithelial cells surrounding these tissues. CCL20 elicits its effects on its target cells by binding and activating the chemokine receptor CCR6.
Chemokine ligand 18 (CCL18) is a small cytokine belonging to the CC chemokine family. The functions of CCL18 have been well studied in laboratory settings, however the physiological effects of the molecule in living organisms have been difficult to characterize because there is no similar protein in rodents that can be studied. The receptor for CCL18 has been identified in humans only recently, which will help scientists understand the molecule's role in the body.
Chemokine ligand 21 (CCL21) is a small cytokine belonging to the CC chemokine family. This chemokine is also known as 6Ckine, exodus-2, and secondary lymphoid-tissue chemokine (SLC). CCL21 elicits its effects by binding to a cell surface chemokine receptor known as CCR7. The main function of CCL21 is to guide CCR7 expressing leukocytes to the secondary lymphoid organs, such as lymph nodes and Peyer´s patches.
CCL17 is a powerful chemokine produced in the thymus and by antigen-presenting cells like dendritic cells, macrophages, and monocytes. CCL17 plays a complex role in cancer. It attracts T-regulatory cells allowing for some cancers to evade an immune response. However, in other cancers, such as melanoma, an increase in CCL17 is linked to an improved outcome. CCL17 has also been linked to autoimmune and allergic diseases.
Chemokine ligand 19 (CCL19) is a protein that in humans is encoded by the CCL19 gene.
Chemokine ligand (XCL1) is a small cytokine belonging to the C chemokine family that is also known as lymphotactin. Chemokines are known for their function in inflammatory and immunological responses. This family C chemokines differs in structure and function from most chemokines. There are only two chemokines in this family and what separated them from other chemokines is that they only have two cysteines; one N-terminal cysteine and one cysteine downstream. These both are called Lymphotactin, alpha and beta form, and claim special characteristics only found between the two. Lymphotactins can go through a reversible conformational change which changes its binding shifts.
Chemokine ligand 2 (XCL2) is a small cytokine belonging to the XC chemokine family that is highly related to another chemokine called XCL1. It is predominantly expressed in activated T cells, but can also be found at low levels in unstimulated cells. XCL2 induces chemotaxis of cells expressing the chemokine receptor XCR1. Its gene is located on chromosome 1 in humans.
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 ligand 19 (CCL19/ELC) and ligand 21 (CCL21). The ligands have similar affinity for the receptor, though CCL19 has been shown to induce internalisation of CCR7 and desensitisation of the cell to CCL19/CCL21 signals. CCR7 is a transmembrane protein with 7 transmembrane domains, which is coupled with heterotrimeric G proteins, which transduce the signal downstream through various signalling cascades. The main function of the receptor is to guide immune cells to immune organs by detecting specific chemokines, which these tissues secrete.
C-C chemokine receptor type 1 is a protein that in humans is encoded by the CCR1 gene.
Chemokine receptor 6 also known as CCR6 is a CC chemokine receptor protein which in humans is encoded by the CCR6 gene. CCR6 has also recently been designated CD196. The gene is located on the long arm of Chromosome 6 (6q27) on the Watson (plus) strand. It is 139,737 bases long and encodes a protein of 374 amino acids.
G-protein coupled receptor 183 also known as Epstein-Barr virus-induced G-protein coupled receptor 2 (EBI2) is a protein (GPCR) expressed on the surface of some immune cells, namely B cells and T cells; in humans it is encoded by the GPR183 gene. Expression of EBI2 is one critical mediator of immune cell localization within lymph nodes, responsible in part for the coordination of B cell, T cell, and dendritic cell movement and interaction following antigen exposure. EBI2 is a receptor for oxysterols. The most potent activator is 7α,25-dihydroxycholesterol (7α,25-OHC), with other oxysterols exhibiting varying affinities for the receptor. Oxysterol gradients drive chemotaxis, attracting the EBI2-expressing cells to locations of high ligand concentration. The GPR183 gene was identified due to its upregulation during Epstein-Barr virus infection of the Burkitt's lymphoma cell line BL41, hence its name: EBI2.
Chemokine receptor 8, also known as CCR8, is a protein which in humans is encoded by the CCR8 gene. CCR8 has also recently been designated CDw198.
Chemokine-binding protein 2 is a protein that in humans is encoded by the CCBP2 gene.
Immunology is the study of the immune system during health and disease. Below is a list of immunology-related articles.
Antigen transfer in the thymus is the transmission of self-antigens between thymic antigen-presenting cells which contributes to the establishment of T cell central tolerance.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.