Alternative titles; symbols
HGNC Approved Gene Symbol: CCR10
Cytogenetic location: 17q21.2 Genomic coordinates (GRCh38): 17:42,678,889-42,681,843 (from NCBI)
Chemokines are a group of small (approximately 8-14 kD), mostly basic, structurally related molecules that regulate cell trafficking of various types of leukocytes through interactions with a subset of 7-transmembrane, G protein-coupled receptors. Chemokines also play fundamental roles in the development, homeostasis, and function of the immune system, and they have effects on cells of the central nervous system as well as on endothelial cells involved in angiogenesis or angiostasis. Chemokines are divided into 2 major subfamilies, CXC and CC, based on the arrangement of the first 2 of the 4 conserved cysteine residues; the 2 cysteines are separated by a single amino acid in CXC chemokines and are adjacent in CC chemokines (summary by Strieter et al., 1995; Zlotnik and Yoshie, 2000). CCR10 is the receptor for CCL27 (SCYA27; 604833); CCR10-CCL27 interactions are involved in T cell-mediated skin inflammation (Homey et al., 2002).
Marchese et al. (1994) cloned a gene with the 7 transmembrane domains characteristic of G protein-coupled receptors. This gene, designated GPR2, was found to encode a protein that most closely resembled interleukin-8 receptor (IL8R1, 146929; IL8R2, 146928); it showed 51% identity in the transmembrane regions. The GPR2 gene was not expressed in 6 brain regions examined.
By screening a human T-cell cDNA library and a human B-cell/T-cell hybrid cDNA library, respectively, Jarmin et al. (2000) and Homey et al. (2000) identified cDNAs encoding GPR2, which they called CCR10. These full-length GPR2 cDNAs encode a protein of 362 amino acids, including 8 N-terminal amino acids missing from the sequence reported by Marchese et al. (1994). Northern blot analysis by Jarmin et al. (2000) detected high-level expression of a 1.4-kb GPR2 transcript in adult testis and small intestine and fetal lung and kidney. Weaker expression was detected in adult spleen, thymus, lymph node, colon, heart, ovary, peripheral blood leukocytes, and spinal cord. A second GPR2 transcript of approximately 2 kb was detected in most of these tissues. Quantitative PCR analysis by Homey et al. (2000) detected GPR2 expression in adult small intestine and colon and fetal liver, lung, spleen, testis, brain, and uterus. Homey et al. (2000) showed that SCYA27 (CCL27; 604833) induces a specific calcium flux and a chemotactic response in cells expressing GPR2. Although SCYA27 is constitutively expressed in normal and inflammatory skin tissues, GPR2 expression is low in these tissues. However, Homey et al. (2000) found that GPR2 is constitutively expressed in skin melanocytes, fibroblasts, and microvascular endothelial cells, and that it is upregulated by IL1B (147720) and TNF (191160). Expression was also detected in T cells, Langerhans cells, and peripheral blood mononuclear cells but not in dendritic cells.
By fluorescence in situ hybridization, Marchese et al. (1994) assigned the GPR2 gene to 17q21.1-q21.3. Wang et al. (2000) mapped the mouse Gpr2 gene to the distal region of chromosome 11 by interspecific backcross analysis.
Using immunohistochemical analysis, Homey et al. (2002) demonstrated expression of CCL27 in normal keratinocytes and its strong upregulation in skin lesions of atopic dermatitis, contact dermatitis, and psoriasis patients. CCR10+ T lymphocytes were detected in lesional but not normal skin of these patients. Flow cytometric analysis showed that CCL27 binds extracellular matrix components and dermal microvascular endothelial cells and fibroblasts and mediates adhesion and transendothelial migration of CCR10+ circulating leukocytes. CCR10 is predominantly expressed on CD4+CLA+ (cutaneous lymphocyte antigen), rather than CD8+, circulating T cells. RT-PCR, confocal microscopy, and ELISA analysis indicated that keratinocytes exposed to TNF or IL1B but not to IL4 (147780) or IFNG (147570) in vitro express increased CCL27.
Homey et al. (2002) injected mice with human CCL27 intradermally. RT-PCR analysis revealed dose-dependent expression of IL2, CCR10, and LFA1A (153370). Immunohistochemical analysis demonstrated that treatment with glucocorticosteroid or anti-Ccl27 markedly reduced skin thickness and leukocyte recruitment in contact hypersensitivity and atopic dermatitis mouse models. Homey et al. (2002) concluded that neutralization of CCL27-CCR10 interactions impairs lymphocyte recruitment and inhibits allergen-induced skin inflammation. They suggested that these molecules could be targets for selective therapy of inflammatory and autoimmune skin diseases.
Homey, B., Alenius, H., Muller, A., Soto, H., Bowman, E. P., Yuan, W., McEvoy, L., Lauerma, A. I., Assmann, T., Bunemann, E., Lehto, M., Wolff, H., Yen, D., Marxhausen, H., To, W., Sedgwick, J., Ruzicka, T., Lehmann, P., Zlotnik, A. CCL27-CCR10 interactions regulate T cell-mediated skin inflammation. Nature Med. 8: 157-165, 2002. [PubMed: 11821900] [Full Text: https://doi.org/10.1038/nm0202-157]
Homey, B., Wang, W., Soto, H., Buchanan, M. E., Wiesenborn, A., Catron, D., Muller, A., McClanahan, T. K., Dieu-Nosjean, M.-C., Orozco, R., Ruzicka, T., Lehmann, P., Oldham, E., Zlotnik, A. Cutting edge: the orphan chemokine receptor G protein-coupled receptor-2 (GPR-2, CCR10) binds the skin-associated chemokine CCL27 (CTACK/ALP/ILC). J. Immun. 164: 3465-3470, 2000. [PubMed: 10725697] [Full Text: https://doi.org/10.4049/jimmunol.164.7.3465]
Jarmin, D. I., Rits, M., Bota, D., Gerard, N. P., Graham, G. J., Clark-Lewis, I., Gerard, C. Cutting edge: identification of the orphan receptor G-protein-coupled receptor 2 as CCR10, a specific receptor for the chemokine ESkine. J. Immun. 164: 3460-3464, 2000. [PubMed: 10725696] [Full Text: https://doi.org/10.4049/jimmunol.164.7.3460]
Marchese, A., Docherty, J. M., Nguyen, T., Heiber, M., Cheng, R., Heng, H. H. Q., Tsui, L.-C., Shi, X., George, S. R., O'Dowd, B. F. Cloning of human genes encoding novel G protein-coupled receptors. Genomics 23: 609-618, 1994. [PubMed: 7851889] [Full Text: https://doi.org/10.1006/geno.1994.1549]
Strieter, R. M., Polverini, P. J., Arenberg, D. A., Kunkel, S. L. The role of CXC chemokines as regulators of angiogenesis. Shock 4: 155-160, 1995. [PubMed: 8574748] [Full Text: https://doi.org/10.1097/00024382-199509000-00001]
Wang, W., Soto, H., Oldham, E. R., Buchanan, M. E., Homey, B., Catron, D., Jenkins, N., Copeland, N. G., Gilbert, D. J., Nguyen, N., Abrams, J., Kershenovich, D., Smith, K., McClanahan, T., Vicari, A. P., Zlotnik, A. Identification of a novel chemokine (CCL28), which binds CCR10 (GPR2). J. Biol. Chem. 275: 22313-22323, 2000. [PubMed: 10781587] [Full Text: https://doi.org/10.1074/jbc.M001461200]
Zlotnik, A., Yoshie, O. Chemokines: a new classification system and their role in immunity. Immunity 12: 121-127, 2000. [PubMed: 10714678] [Full Text: https://doi.org/10.1016/s1074-7613(00)80165-x]