Biology:C-C chemokine receptor type 6
 Generic protein structure example |
Chemokine receptor 6 also known as CCR6 is a CC chemokine receptor protein which in humans is encoded by the CCR6 gene.[1] CCR6 has also recently been designated CD196 (cluster of differentiation 196). 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 (molecular weight 42,494 Da).[1]
Function
This protein belongs to family A of G protein-coupled receptor superfamily. The gene is expressed in lymphatic and non-lymphatic tissue as spleen, lymph nodes, pancreas, colon, appendix, small intestine. CCR6 is expressed on B-cells, immature dendritic cells (DC), T-cells (Th1, Th2, Th17, Treg), natural killer T cells (NKT cells) and neutrophils.[2] The ligand of this receptor is CCL20 or in the other name - macrophage inflammatory protein 3 alpha (MIP-3 alpha). This chemokine receptor is special because it binds only one chemokine ligand CCL20 in compare to other chemokine receptors.[3] CCR6 has a key role in connection between immature DC an adaptive immunity.[4] This receptor has been shown to be important for B-lineage maturation and antigen-driven B-cell differentiation, and it may regulate the migration and recruitment of dendritic cells and T cells during inflammatory and immunological responses. Alternatively spliced transcript variants that encode the same protein have been described for this gene.[5]
Interleukin 4 (IL-4) and interferon gamma (IFNγ) suppress expression of CCR6 in langerhans cells development and interleukin 10 (IL-10) induces the expression. It can regulate immune response in inflammatory tissue.[6]
Proinflammatory Th17 cells express CCR6 and its ligand CCL20. CCR6 influences their migration to sites of inflammation. Some Th17 cells migrate via chemokine gradient of CCL20 to inflammatory sites and themselves can express more CCL20 to bring in more Th17 cells and regulatory T-cells (Treg). This can lead to chronic inflammation. In some models, the lack of CCR6 leads to less severe autoimmune encephalomyelitis.[7]
Clinical significance
CCR6 has a function in development and metastatic spread of gastrointestinal malignancies.[3] Expression of CCR6 was found to be up-regulated in colorectal cancer.[8] Many patients with colorectal cancer have liver metastases. Colorectal carcinoma cells express CCR6 and CCL20. High level of CCL20 in liver chemoattract colorectal carcinoma cells and cause metastases in liver.[3][9] Novel research has identified a microRNA that is able to downregulate CCR6 in cancer cell lines.[10]
CCR6 has been associated with Crohn's disease.[11]
References
- ↑ 1.0 1.1 "Molecular cloning and RNA expression of two new human chemokine receptor-like genes". Biochem. Biophys. Res. Commun. 227 (3): 846–53. October 1996. doi:10.1006/bbrc.1996.1595. PMID 8886020.
- ↑ Schutyser, Evemie; Struyf, Sofie; Van Damme, Jo (October 2003). "The CC chemokine CCL20 and its receptor CCR6". Cytokine & Growth Factor Reviews 14 (5): 409–426. doi:10.1016/s1359-6101(03)00049-2. ISSN 1359-6101. PMID 12948524.
- ↑ 3.0 3.1 3.2 Frick, Vilma Oliveira; Rubie, Claudia; Keilholz, Ulrich; Ghadjar, Pirus (2016-01-14). "Chemokine/chemokine receptor pair CCL20/CCR6 in human colorectal malignancy: An overview". World Journal of Gastroenterology 22 (2): 833–841. doi:10.3748/wjg.v22.i2.833. ISSN 2219-2840. PMID 26811629.
- ↑ Dieu, M. C.; Vanbervliet, B.; Vicari, A.; Bridon, J. M.; Oldham, E.; Aït-Yahia, S.; Brière, F.; Zlotnik, A. et al. (1998-07-20). "Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites". The Journal of Experimental Medicine 188 (2): 373–386. doi:10.1084/jem.188.2.373. ISSN 0022-1007. PMID 9670049.
- ↑ "Entrez Gene: CCR6 chemokine (C-C motif) receptor 6". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1235.
- ↑ Dieu-Nosjean, Marie-Caroline; Massacrier, Catherine; Vanbervliet, Béatrice; Fridman, Wolf-Herman; Caux, Christophe (2001-11-15). "IL-10 Induces CCR6 Expression During Langerhans Cell Development While IL-4 and IFN-γ Suppress It" (in en). The Journal of Immunology 167 (10): 5594–5602. doi:10.4049/jimmunol.167.10.5594. ISSN 0022-1767. PMID 11698430.
- ↑ Yamazaki, Tomohide; Yang, Xuexian O.; Chung, Yeonseok; Fukunaga, Atsushi; Nurieva, Roza; Pappu, Bhanu; Martin-Orozco, Natalia; Kang, Hong Soon et al. (2008-12-15). "CCR6 Regulates the Migration of Inflammatory and Regulatory T Cells" (in en). The Journal of Immunology 181 (12): 8391–8401. doi:10.4049/jimmunol.181.12.8391. ISSN 0022-1767. PMID 19050256.
- ↑ Rubie, Claudia; Kruse, Bianca; Frick, Vilma Oliveira; Kölsch, Kathrin; Ghadjar, Pirus; Wagner, Mathias; Grässer, Friedrich; Wagenpfeil, Stefan et al. (2014-02-21). "Chemokine receptor CCR6 expression is regulated by miR-518a-5p in colorectal cancer cells". Journal of Translational Medicine 12: 48. doi:10.1186/1479-5876-12-48. ISSN 1479-5876. PMID 24559209.
- ↑ Frick, V. O.; .Rubie, C.; Kölsch, K.; Wagner, M.; Ghadjar, P.; Graeber, S.; Glanemann, M. (September 2013). "CCR6/CCL20 Chemokine Expression Profile in Distinct Colorectal Malignancies" (in en). Scandinavian Journal of Immunology 78 (3): 298–305. doi:10.1111/sji.12087. PMID 23790181.
- ↑ Rubie C (Feb 2014). "Chemokine receptor CCR6 expression is regulated by miR-518a-5p in colorectal cancer cells.". J Transl Med 12: 48. doi:10.1186/1479-5876-12-48. PMID 24559209.
- ↑ "Diverse Genome-wide Association Studies Associate the IL12/IL23 Pathway with Crohn Disease". Am. J. Hum. Genet. 84 (3): 399–405. February 2009. doi:10.1016/j.ajhg.2009.01.026. PMID 19249008.
External links
- Human CCR6 genome location and CCR6 gene details page in the UCSC Genome Browser.
- "Chemokine Receptors: CCR6". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2230.
Further reading
- "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1–2): 171–4. 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- "Molecular cloning and RNA expression of two new human chemokine receptor-like genes". Biochem. Biophys. Res. Commun. 227 (3): 846–53. 1996. doi:10.1006/bbrc.1996.1595. PMID 8886020.
- "Cloning of STRL22, a new human gene encoding a G-protein-coupled receptor related to chemokine receptors and located on chromosome 6q27". Genomics 40 (1): 175–80. 1997. doi:10.1006/geno.1996.4544. PMID 9070937. https://zenodo.org/record/1229715.
- "Identification of CCR6, the specific receptor for a novel lymphocyte-directed CC chemokine LARC". J. Biol. Chem. 272 (23): 14893–8. 1997. doi:10.1074/jbc.272.23.14893. PMID 9169459.
- "A somatic cell hybrid panel for distal 17q: GDIA1 maps to 17q25.3". Cytogenet. Cell Genet. 76 (3–4): 172–5. 1997. doi:10.1159/000134538. PMID 9186513.
- "STRL22 is a receptor for the CC chemokine MIP-3alpha". Biochem. Biophys. Res. Commun. 236 (1): 212–7. 1997. doi:10.1006/bbrc.1997.6936. PMID 9223454. https://zenodo.org/record/1229484.
- "Cloning and characterization of a specific receptor for the novel CC chemokine MIP-3alpha from lung dendritic cells". J. Exp. Med. 186 (6): 825–35. 1997. doi:10.1084/jem.186.6.825. PMID 9294137.
- "CCR6, a CC chemokine receptor that interacts with macrophage inflammatory protein 3alpha and is highly expressed in human dendritic cells". J. Exp. Med. 186 (6): 837–44. 1997. doi:10.1084/jem.186.6.837. PMID 9294138.
- "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- "Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6". Science 286 (5439): 525–8. 1999. doi:10.1126/science.286.5439.525. PMID 10521347.
- "Regulation of CCR6 chemokine receptor expression and responsiveness to macrophage inflammatory protein-3alpha/CCL20 in human B cells". Blood 96 (7): 2338–45. 2000. doi:10.1182/blood.V96.7.2338. PMID 11001880.
- "Chemokine receptor expression by human syncytiotrophoblast". J. Reprod. Immunol. 49 (2): 97–114. 2001. doi:10.1016/S0165-0378(00)00083-8. PMID 11164896.
- "Mediators of innate immunity that target immature, but not mature, dendritic cells induce antitumor immunity when genetically fused with nonimmunogenic tumor antigens". J. Immunol. 167 (11): 6644–53. 2002. doi:10.4049/jimmunol.167.11.6644. PMID 11714836.
- "Up-regulation of CCR5 and CCR6 on distinct subpopulations of antigen-activated CD4+ T lymphocytes". J. Immunol. 168 (1): 65–72. 2002. doi:10.4049/jimmunol.168.1.65. PMID 11751947.
- "Human B cells become highly responsive to macrophage-inflammatory protein-3 alpha/CC chemokine ligand-20 after cellular activation without changes in CCR6 expression or ligand binding". J. Immunol. 168 (10): 4871–80. 2002. doi:10.4049/jimmunol.168.10.4871. PMID 11994436.
- "Macrophage inflammatory protein 3alpha-CC chemokine receptor 6 interactions play an important role in CD4+ T-cell accumulation in periodontal diseased tissue". Clin. Exp. Immunol. 128 (3): 548–54. 2002. doi:10.1046/j.1365-2249.2002.01865.x. PMID 12067311.
- "Trafficking machinery of NKT cells: shared and differential chemokine receptor expression among V alpha 24(+)V beta 11(+) NKT cell subsets with distinct cytokine-producing capacity". Blood 100 (1): 11–6. 2002. doi:10.1182/blood-2001-12-0196. PMID 12070001.
- "Mutating the four extracellular cysteines in the chemokine receptor CCR6 reveals their differing roles in receptor trafficking, ligand binding, and signaling". Biochemistry 41 (26): 8332–41. 2002. doi:10.1021/bi025855y. PMID 12081481.
- "The structure of human macrophage inflammatory protein-3alpha /CCL20. Linking antimicrobial and CC chemokine receptor-6-binding activities with human beta-defensins". J. Biol. Chem. 277 (40): 37647–54. 2002. doi:10.1074/jbc.M203907200. PMID 12149255.
- "CCR6 colocalizes with CD18 and enhances adhesion to activated endothelial cells in CCR6-transduced Jurkat T cells". J. Immunol. 169 (5): 2346–53. 2002. doi:10.4049/jimmunol.169.5.2346. PMID 12193700.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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