Chemokine receptor 6 also known as CCR6 is a CC chemokine receptor protein which in humans is encoded by the CCR6 gene.[5] 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).[5]
Function
editThis 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.[6] 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.[7] CCR6 has a key role in connection between immature DC an adaptive immunity.[8] 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.[9]
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.[10]
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.[11]
Clinical significance
editCCR6 has a function in development and metastatic spread of gastrointestinal malignancies.[7] Expression of CCR6 was found to be up-regulated in colorectal cancer.[12] 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.[7][13] Novel research has identified a microRNA that is able to downregulate CCR6 in cancer cell lines.[14]
CCR6 has been associated with Crohn's disease.[15]
References
edit- ^ a b c GRCh38: Ensembl release 89: ENSG00000112486 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000040899 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b Zaballos A, Varona R, Gutiérrez J, Lind P, Márquez G (October 1996). "Molecular cloning and RNA expression of two new human chemokine receptor-like genes". Biochemical and Biophysical Research Communications. 227 (3): 846–853. doi:10.1006/bbrc.1996.1595. PMID 8886020.
- ^ Schutyser E, Struyf S, Van Damme J (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. PMID 12948524.
- ^ a b c Frick VO, Rubie C, Keilholz U, Ghadjar P (January 2016). "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. PMC 4716081. PMID 26811629.
- ^ Dieu MC, Vanbervliet B, Vicari A, Bridon JM, Oldham E, Aït-Yahia S, et al. (July 1998). "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. PMC 2212459. PMID 9670049.
- ^ "Entrez Gene: CCR6 chemokine (C-C motif) receptor 6".
- ^ Dieu-Nosjean MC, Massacrier C, Vanbervliet B, Fridman WH, Caux C (November 2001). "IL-10 induces CCR6 expression during Langerhans cell development while IL-4 and IFN-gamma suppress it". Journal of Immunology. 167 (10): 5594–5602. doi:10.4049/jimmunol.167.10.5594. PMID 11698430.
- ^ Yamazaki T, Yang XO, Chung Y, Fukunaga A, Nurieva R, Pappu B, et al. (December 2008). "CCR6 regulates the migration of inflammatory and regulatory T cells". Journal of Immunology. 181 (12): 8391–8401. doi:10.4049/jimmunol.181.12.8391. PMC 2752441. PMID 19050256.
- ^ Rubie C, Kruse B, Frick VO, Kölsch K, Ghadjar P, Wagner M, et al. (February 2014). "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. PMC 3996063. PMID 24559209.
- ^ Frick VO, Rubie C, Kölsch K, Wagner M, Ghadjar P, Graeber S, et al. (September 2013). "CCR6/CCL20 chemokine expression profile in distinct colorectal malignancies". Scandinavian Journal of Immunology. 78 (3): 298–305. doi:10.1111/sji.12087. PMID 23790181. S2CID 45126701.
- ^ Rubie C, Kruse B, Frick VO, Kölsch K, Ghadjar P, Wagner M, et al. (February 2014). "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. PMC 3996063. PMID 24559209.
- ^ Wang K, Zhang H, Kugathasan S, Annese V, Bradfield JP, Russell RK, et al. (March 2009). "Diverse genome-wide association studies associate the IL12/IL23 pathway with Crohn Disease". American Journal of Human Genetics. 84 (3): 399–405. doi:10.1016/j.ajhg.2009.01.026. PMC 2668006. PMID 19249008.
External links
edit- 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.
Further reading
edit- Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Zaballos A, Varona R, Gutiérrez J, Lind P, Márquez G (October 1996). "Molecular cloning and RNA expression of two new human chemokine receptor-like genes". Biochemical and Biophysical Research Communications. 227 (3): 846–853. doi:10.1006/bbrc.1996.1595. PMID 8886020.
- Liao F, Lee HH, Farber JM (February 1997). "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): 175–180. doi:10.1006/geno.1996.4544. PMID 9070937.
- Baba M, Imai T, Nishimura M, Kakizaki M, Takagi S, Hieshima K, et al. (June 1997). "Identification of CCR6, the specific receptor for a novel lymphocyte-directed CC chemokine LARC". The Journal of Biological Chemistry. 272 (23): 14893–14898. doi:10.1074/jbc.272.23.14893. PMID 9169459.
- Wagner T, Tommerup N, Wirth J, Leffers H, Zimmer J, Back E, et al. (1997). "A somatic cell hybrid panel for distal 17q: GDIA1 maps to 17q25.3". Cytogenetics and Cell Genetics. 76 (3–4): 172–175. doi:10.1159/000134538. PMID 9186513.
- Liao F, Alderson R, Su J, Ullrich SJ, Kreider BL, Farber JM (July 1997). "STRL22 is a receptor for the CC chemokine MIP-3alpha". Biochemical and Biophysical Research Communications. 236 (1): 212–217. doi:10.1006/bbrc.1997.6936. PMID 9223454.
- Power CA, Church DJ, Meyer A, Alouani S, Proudfoot AE, Clark-Lewis I, et al. (September 1997). "Cloning and characterization of a specific receptor for the novel CC chemokine MIP-3alpha from lung dendritic cells". The Journal of Experimental Medicine. 186 (6): 825–835. doi:10.1084/jem.186.6.825. PMC 2199050. PMID 9294137.
- Greaves DR, Wang W, Dairaghi DJ, Dieu MC, Saint-Vis B, Franz-Bacon K, et al. (September 1997). "CCR6, a CC chemokine receptor that interacts with macrophage inflammatory protein 3alpha and is highly expressed in human dendritic cells". The Journal of Experimental Medicine. 186 (6): 837–844. doi:10.1084/jem.186.6.837. PMC 2199049. PMID 9294138.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J, et al. (October 1999). "Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6". Science. 286 (5439): 525–528. doi:10.1126/science.286.5439.525. PMID 10521347.
- Krzysiek R, Lefevre EA, Bernard J, Foussat A, Galanaud P, Louache F, et al. (October 2000). "Regulation of CCR6 chemokine receptor expression and responsiveness to macrophage inflammatory protein-3alpha/CCL20 in human B cells". Blood. 96 (7): 2338–2345. doi:10.1182/blood.V96.7.2338. PMID 11001880.
- Douglas GC, Thirkill TL, Sideris V, Rabieh M, Trollinger D, Nuccitelli R (February 2001). "Chemokine receptor expression by human syncytiotrophoblast". Journal of Reproductive Immunology. 49 (2): 97–114. doi:10.1016/S0165-0378(00)00083-8. PMID 11164896.
- Biragyn A, Surenhu M, Yang D, Ruffini PA, Haines BA, Klyushnenkova E, et al. (December 2001). "Mediators of innate immunity that target immature, but not mature, dendritic cells induce antitumor immunity when genetically fused with nonimmunogenic tumor antigens". Journal of Immunology. 167 (11): 6644–6653. doi:10.4049/jimmunol.167.11.6644. PMID 11714836.
- Ebert LM, McColl SR (January 2002). "Up-regulation of CCR5 and CCR6 on distinct subpopulations of antigen-activated CD4+ T lymphocytes". Journal of Immunology. 168 (1): 65–72. doi:10.4049/jimmunol.168.1.65. PMID 11751947.
- Liao F, Shirakawa AK, Foley JF, Rabin RL, Farber JM (May 2002). "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". Journal of Immunology. 168 (10): 4871–4880. doi:10.4049/jimmunol.168.10.4871. PMID 11994436.
- Hosokawa Y, Nakanishi T, Yamaguchi D, Takahashi K, Yumoto H, Ozaki K, et al. (June 2002). "Macrophage inflammatory protein 3alpha-CC chemokine receptor 6 interactions play an important role in CD4+ T-cell accumulation in periodontal diseased tissue". Clinical and Experimental Immunology. 128 (3): 548–554. doi:10.1046/j.1365-2249.2002.01865.x. PMC 1906256. PMID 12067311.
- Kim CH, Johnston B, Butcher EC (July 2002). "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): 11–16. doi:10.1182/blood-2001-12-0196. PMID 12070001. S2CID 37076470.
- Ai LS, Liao F (July 2002). "Mutating the four extracellular cysteines in the chemokine receptor CCR6 reveals their differing roles in receptor trafficking, ligand binding, and signaling". Biochemistry. 41 (26): 8332–8341. doi:10.1021/bi025855y. PMID 12081481.
- Hoover DM, Boulegue C, Yang D, Oppenheim JJ, Tucker K, Lu W, et al. (October 2002). "The structure of human macrophage inflammatory protein-3alpha /CCL20. Linking antimicrobial and CC chemokine receptor-6-binding activities with human beta-defensins". The Journal of Biological Chemistry. 277 (40): 37647–37654. doi:10.1074/jbc.M203907200. PMID 12149255.
- Maki W, Morales RE, Carroll VA, Telford WG, Knibbs RN, Stoolman LM, et al. (September 2002). "CCR6 colocalizes with CD18 and enhances adhesion to activated endothelial cells in CCR6-transduced Jurkat T cells". Journal of Immunology. 169 (5): 2346–2353. doi:10.4049/jimmunol.169.5.2346. PMID 12193700.
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