XCR1

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XCR1
Identifiers
AliasesXCR1, CCGPR5, X-C motif chemokine receptor 1
External IDsOMIM: 600552 MGI: 1346338 HomoloGene: 21095 GeneCards: XCR1
Gene location (Human)
Chromosome 3 (human)
Chr.Chromosome 3 (human)[1]
Chromosome 3 (human)
Genomic location for XCR1
Genomic location for XCR1
Band3p21.31Start46,017,024 bp[1]
End46,027,742 bp[1]
RNA expression pattern
PBB GE XCR1 221468 at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_005283
NM_001024644

NM_011798

RefSeq (protein)

NP_001019815
NP_005274

n/a

Location (UCSC)Chr 3: 46.02 – 46.03 MbChr 9: 123.85 – 123.86 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.

Function[edit]

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.[8]

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 a important regulator of XCL1 production.[9]

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. [10]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000173578 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000060509 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: XCR1 chemokine (C motif) receptor 1".
  6. ^ Becker M, Güttler S, Bachem A, Hartung E, Mora A, Jäkel A, Hutloff A, Henn V, Mages HW, Gurka S, Kroczek RA. "Ontogenic, Phenotypic, and Functional Characterization of XCR1(+) Dendritic Cells Leads to a Consistent Classification of Intestinal Dendritic Cells Based on the Expression of XCR1 and SIRPα". Frontiers in Immunology. 5: 326. doi:10.3389/fimmu.2014.00326. PMC 4112810. PMID 25120540.
  7. ^ Kroczek RA, Henn V. "The Role of XCR1 and its Ligand XCL1 in Antigen Cross-Presentation by Murine and Human Dendritic Cells". Frontiers in Immunology. 3: 14. doi:10.3389/fimmu.2012.00014. PMC 3342032. PMID 22566900.
  8. ^ Becker M, Güttler S, Bachem A, Hartung E, Mora A, Jäkel A, Hutloff A, Henn V, Mages HW, Gurka S, Kroczek RA. "Ontogenic, Phenotypic, and Functional Characterization of XCR1(+) Dendritic Cells Leads to a Consistent Classification of Intestinal Dendritic Cells Based on the Expression of XCR1 and SIRPα". Frontiers in Immunology. 5: 326. doi:10.3389/fimmu.2014.00326. PMC 4112810. PMID 25120540.
  9. ^ Lei Y, Ripen AM, Ishimaru N, Ohigashi I, Nagasawa T, Jeker LT, Bösl MR, Holländer GA, Hayashi Y, Malefyt Rde W, Nitta T, Takahama Y (February 2011). "Aire-dependent production of XCL1 mediates medullary accumulation of thymic dendritic cells and contributes to regulatory T cell development". The Journal of Experimental Medicine. 208 (2): 383–94. doi:10.1084/jem.20102327. PMC 3039864. PMID 21300913.
  10. ^ Alexandre YO, Ghilas S, Sanchez C, Le Bon A, Crozat K, Dalod M (January 2016). "XCR1+ dendritic cells promote memory CD8+ T cell recall upon secondary infections with Listeria monocytogenes or certain viruses". The Journal of Experimental Medicine. 213 (1): 75–92. doi:10.1084/jem.20142350. PMC 4710197. PMID 26694969.

External links[edit]

Further reading[edit]

  • Maghazachi AA (June 1999). "Intracellular signalling pathways induced by chemokines in natural killer cells". Cellular Signalling. 11 (6): 385–90. doi:10.1016/S0898-6568(99)00008-X. PMID 10400311.
  • Gao JL, Kuhns DB, Tiffany HL, McDermott D, Li X, Francke U, Murphy PM (May 1993). "Structure and functional expression of the human macrophage inflammatory protein 1 alpha/RANTES receptor". The Journal of Experimental Medicine. 177 (5): 1421–7. doi:10.1084/jem.177.5.1421. PMC 2191019. PMID 7683036.
  • Heiber M, Docherty JM, Shah G, Nguyen T, Cheng R, Heng HH, Marchese A, Tsui LC, Shi X, George SR (January 1995). "Isolation of three novel human genes encoding G protein-coupled receptors". DNA and Cell Biology. 14 (1): 25–35. doi:10.1089/dna.1995.14.25. PMID 7832990.
  • Yoshida T, Imai T, Kakizaki M, Nishimura M, Takagi S, Yoshie O (June 1998). "Identification of single C motif-1/lymphotactin receptor XCR1". The Journal of Biological Chemistry. 273 (26): 16551–4. doi:10.1074/jbc.273.26.16551. PMID 9632725.
  • Shan L, Qiao X, Oldham E, Catron D, Kaminski H, Lundell D, Zlotnik A, Gustafson E, Hedrick JA (February 2000). "Identification of viral macrophage inflammatory protein (vMIP)-II as a ligand for GPR5/XCR1". Biochemical and Biophysical Research Communications. 268 (3): 938–41. doi:10.1006/bbrc.2000.2235. PMID 10679309.
  • Maho A, Bensimon A, Vassart G, Parmentier M (2000). "Mapping of the CCXCR1, CX3CR1, CCBP2 and CCR9 genes to the CCR cluster within the 3p21.3 region of the human genome". Cytogenetics and Cell Genetics. 87 (3–4): 265–8. doi:10.1159/000015443. PMID 10702689.
  • Kurt RA, Bauck M, Harma S, McCulloch K, Baher A, Urba WJ (May 2001). "Role of C chemokine lymphotactin in mediating recruitment of antigen-specific CD62L(lo) cells in vitro and in vivo". Cellular Immunology. 209 (2): 83–8. doi:10.1006/cimm.2001.1790. PMID 11446740.
  • Shinkai H, Morozumi T, Toki D, Eguchi-Ogawa T, Muneta Y, Awata T, Uenishi H (April 2005). "Genomic structure of eight porcine chemokine receptors and intergene sharing of an exon between CCR1 and XCR1". Gene. 349: 55–66. doi:10.1016/j.gene.2004.10.017. PMID 15777643.
  • Lüttichau HR, Johnsen AH, Jurlander J, Rosenkilde MM, Schwartz TW (June 2007). "Kaposi sarcoma-associated herpes virus targets the lymphotactin receptor with both a broad spectrum antagonist vCCL2 and a highly selective and potent agonist vCCL3". The Journal of Biological Chemistry. 282 (24): 17794–805. doi:10.1074/jbc.M702001200. PMID 17403668.

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.