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.[1]
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.[2]
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 CD4+ and CD8+ may become outdated terms, since the activity of the cell appears to be primarily dependent upon the expression of XCR1, which will make a population far more similar than the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.[3]
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.[4]
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.[5]
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. [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. PMID25120540.
↑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. PMID22566900.
↑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. PMID25120540.
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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. PMID9632725.
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. PMID10679309.
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. PMID10702689.
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. PMID11446740.
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. PMID15777643.
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. PMID17403668.
