{{Short description|Mammalian protein found in humans}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox_gene}} '''Chemokine receptor 6''' also known as '''CCR6''' is a CC chemokine receptor protein which in humans is encoded by the ''CCR6'' gene.<ref name="pmid8886020">{{cite journal | vauthors = Zaballos A, Varona R, Gutiérrez J, Lind P, Márquez G | title = Molecular cloning and RNA expression of two new human chemokine receptor-like genes | journal = Biochemical and Biophysical Research Communications | volume = 227 | issue = 3 | pages = 846–853 | date = October 1996 | pmid = 8886020 | doi = 10.1006/bbrc.1996.1595 | bibcode = 1996BBRC..227..846Z }}</ref> 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).<ref name="pmid8886020" />
== 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.<ref>{{cite journal | vauthors = Schutyser E, Struyf S, Van Damme J | title = The CC chemokine CCL20 and its receptor CCR6 | journal = Cytokine & Growth Factor Reviews | volume = 14 | issue = 5 | pages = 409–426 | date = October 2003 | pmid = 12948524 | doi = 10.1016/s1359-6101(03)00049-2 }}</ref> 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 comparison to other chemokine receptors.<ref name="Frick 833–841">{{cite journal | vauthors = Frick VO, Rubie C, Keilholz U, Ghadjar P | title = Chemokine/chemokine receptor pair CCL20/CCR6 in human colorectal malignancy: An overview | journal = World Journal of Gastroenterology | volume = 22 | issue = 2 | pages = 833–841 | date = January 2016 | pmid = 26811629 | pmc = 4716081 | doi = 10.3748/wjg.v22.i2.833 | doi-access = free }}</ref> CCR6 has a key role between immature DC and adaptive immunity.<ref>{{cite journal | vauthors = Dieu MC, Vanbervliet B, Vicari A, Bridon JM, Oldham E, Aït-Yahia S, Brière F, Zlotnik A, Lebecque S, Caux C | title = Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites | journal = The Journal of Experimental Medicine | volume = 188 | issue = 2 | pages = 373–386 | date = July 1998 | pmid = 9670049 | pmc = 2212459 | doi = 10.1084/jem.188.2.373 }}</ref> 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.<ref>{{cite web | title = Entrez Gene: CCR6 chemokine (C-C motif) receptor 6| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=1235}}</ref>
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.<ref>{{cite journal | vauthors = Dieu-Nosjean MC, Massacrier C, Vanbervliet B, Fridman WH, Caux C | title = IL-10 induces CCR6 expression during Langerhans cell development while IL-4 and IFN-gamma suppress it | journal = Journal of Immunology | volume = 167 | issue = 10 | pages = 5594–5602 | date = November 2001 | pmid = 11698430 | doi = 10.4049/jimmunol.167.10.5594 | doi-access = free }}</ref>
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.<ref>{{cite journal | vauthors = Yamazaki T, Yang XO, Chung Y, Fukunaga A, Nurieva R, Pappu B, Martin-Orozco N, Kang HS, Ma L, Panopoulos AD, Craig S, Watowich SS, Jetten AM, Tian Q, Dong C | title = CCR6 regulates the migration of inflammatory and regulatory T cells | journal = Journal of Immunology | volume = 181 | issue = 12 | pages = 8391–8401 | date = December 2008 | pmid = 19050256 | pmc = 2752441 | doi = 10.4049/jimmunol.181.12.8391 }}</ref>
== Clinical significance == CCR6 has a function in development and metastatic spread of gastrointestinal malignancies.<ref name="Frick 833–841"/> Expression of CCR6 was found to be up-regulated in colorectal cancer.<ref>{{cite journal | vauthors = Rubie C, Kruse B, Frick VO, Kölsch K, Ghadjar P, Wagner M, Grässer F, Wagenpfeil S, Glanemann M | title = Chemokine receptor CCR6 expression is regulated by miR-518a-5p in colorectal cancer cells | journal = Journal of Translational Medicine | volume = 12 | pages = 48 | date = February 2014 | pmid = 24559209 | pmc = 3996063 | doi = 10.1186/1479-5876-12-48 | doi-access = free }}</ref> 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.<ref name="Frick 833–841"/><ref>{{cite journal | vauthors = Frick VO, Rubie C, Kölsch K, Wagner M, Ghadjar P, Graeber S, Glanemann M | title = CCR6/CCL20 chemokine expression profile in distinct colorectal malignancies | journal = Scandinavian Journal of Immunology | volume = 78 | issue = 3 | pages = 298–305 | date = September 2013 | pmid = 23790181 | doi = 10.1111/sji.12087 | s2cid = 45126701 | doi-access = free }}</ref> Novel research has identified a microRNA that is able to downregulate CCR6 in cancer cell lines.<ref name="pmid = 24559209">{{cite journal | vauthors = Rubie C, Kruse B, Frick VO, Kölsch K, Ghadjar P, Wagner M, Grässer F, Wagenpfeil S, Glanemann M | title = Chemokine receptor CCR6 expression is regulated by miR-518a-5p in colorectal cancer cells | journal = Journal of Translational Medicine | volume = 12 | pages = 48 | date = February 2014 | pmid = 24559209 | pmc = 3996063 | doi = 10.1186/1479-5876-12-48 | doi-access = free }}</ref>
CCR6 has been associated with Crohn's disease.<ref name="pmid19249008">{{cite journal | vauthors = Wang K, Zhang H, Kugathasan S, Annese V, Bradfield JP, Russell RK, Sleiman PM, Imielinski M, Glessner J, Hou C, Wilson DC, Walters T, Kim C, Frackelton EC, Lionetti P, Barabino A, Van Limbergen J, Guthery S, Denson L, Piccoli D, Li M, Dubinsky M, Silverberg M, Griffiths A, Grant SF, Satsangi J, Baldassano R, Hakonarson H | title = Diverse genome-wide association studies associate the IL12/IL23 pathway with Crohn Disease | journal = American Journal of Human Genetics | volume = 84 | issue = 3 | pages = 399–405 | date = March 2009 | pmid = 19249008 | pmc = 2668006 | doi = 10.1016/j.ajhg.2009.01.026 }}</ref>
== References == {{reflist}}
== External links == * {{UCSC gene info|CCR6}} * {{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2230 | title = Chemokine Receptors: CCR6 | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | access-date = 2008-12-03 | archive-date = 2008-06-07 | archive-url = https://web.archive.org/web/20080607150542/http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2230 | url-status = dead }}
== Further reading == {{refbegin | 2}} * {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–174 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }} * {{cite journal | vauthors = Zaballos A, Varona R, Gutiérrez J, Lind P, Márquez G | title = Molecular cloning and RNA expression of two new human chemokine receptor-like genes | journal = Biochemical and Biophysical Research Communications | volume = 227 | issue = 3 | pages = 846–853 | date = October 1996 | pmid = 8886020 | doi = 10.1006/bbrc.1996.1595 | bibcode = 1996BBRC..227..846Z }} * {{cite journal | vauthors = Liao F, Lee HH, Farber JM | title = Cloning of STRL22, a new human gene encoding a G-protein-coupled receptor related to chemokine receptors and located on chromosome 6q27 | journal = Genomics | volume = 40 | issue = 1 | pages = 175–180 | date = February 1997 | pmid = 9070937 | doi = 10.1006/geno.1996.4544 }} * {{cite journal | vauthors = Baba M, Imai T, Nishimura M, Kakizaki M, Takagi S, Hieshima K, Nomiyama H, Yoshie O | title = Identification of CCR6, the specific receptor for a novel lymphocyte-directed CC chemokine LARC | journal = The Journal of Biological Chemistry | volume = 272 | issue = 23 | pages = 14893–14898 | date = June 1997 | pmid = 9169459 | doi = 10.1074/jbc.272.23.14893 | doi-access = free }} * {{cite journal | vauthors = Wagner T, Tommerup N, Wirth J, Leffers H, Zimmer J, Back E, Weissenbach J, Scherer G | title = A somatic cell hybrid panel for distal 17q: GDIA1 maps to 17q25.3 | journal = Cytogenetics and Cell Genetics | volume = 76 | issue = 3–4 | pages = 172–175 | year = 1997 | pmid = 9186513 | doi = 10.1159/000134538 }} * {{cite journal | vauthors = Liao F, Alderson R, Su J, Ullrich SJ, Kreider BL, Farber JM | title = STRL22 is a receptor for the CC chemokine MIP-3alpha | journal = Biochemical and Biophysical Research Communications | volume = 236 | issue = 1 | pages = 212–217 | date = July 1997 | pmid = 9223454 | doi = 10.1006/bbrc.1997.6936 | bibcode = 1997BBRC..236..212L }} * {{cite journal | vauthors = Power CA, Church DJ, Meyer A, Alouani S, Proudfoot AE, Clark-Lewis I, Sozzani S, Mantovani A, Wells TN | title = Cloning and characterization of a specific receptor for the novel CC chemokine MIP-3alpha from lung dendritic cells | journal = The Journal of Experimental Medicine | volume = 186 | issue = 6 | pages = 825–835 | date = September 1997 | pmid = 9294137 | pmc = 2199050 | doi = 10.1084/jem.186.6.825 }} * {{cite journal | vauthors = Greaves DR, Wang W, Dairaghi DJ, Dieu MC, Saint-Vis B, Franz-Bacon K, Rossi D, Caux C, McClanahan T, Gordon S, Zlotnik A, Schall TJ | title = CCR6, a CC chemokine receptor that interacts with macrophage inflammatory protein 3alpha and is highly expressed in human dendritic cells | journal = The Journal of Experimental Medicine | volume = 186 | issue = 6 | pages = 837–844 | date = September 1997 | pmid = 9294138 | pmc = 2199049 | doi = 10.1084/jem.186.6.837 }} * {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–156 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }} * {{cite journal | vauthors = Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J, Anderson M, Schröder JM, Wang JM, Howard OM, Oppenheim JJ | title = Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6 | journal = Science | volume = 286 | issue = 5439 | pages = 525–528 | date = October 1999 | pmid = 10521347 | doi = 10.1126/science.286.5439.525 }} * {{cite journal | vauthors = Krzysiek R, Lefevre EA, Bernard J, Foussat A, Galanaud P, Louache F, Richard Y | title = Regulation of CCR6 chemokine receptor expression and responsiveness to macrophage inflammatory protein-3alpha/CCL20 in human B cells | journal = Blood | volume = 96 | issue = 7 | pages = 2338–2345 | date = October 2000 | pmid = 11001880 | doi = 10.1182/blood.V96.7.2338 }} * {{cite journal | vauthors = Douglas GC, Thirkill TL, Sideris V, Rabieh M, Trollinger D, Nuccitelli R | title = Chemokine receptor expression by human syncytiotrophoblast | journal = Journal of Reproductive Immunology | volume = 49 | issue = 2 | pages = 97–114 | date = February 2001 | pmid = 11164896 | doi = 10.1016/S0165-0378(00)00083-8 }} * {{cite journal | vauthors = Biragyn A, Surenhu M, Yang D, Ruffini PA, Haines BA, Klyushnenkova E, Oppenheim JJ, Kwak LW | title = Mediators of innate immunity that target immature, but not mature, dendritic cells induce antitumor immunity when genetically fused with nonimmunogenic tumor antigens | journal = Journal of Immunology | volume = 167 | issue = 11 | pages = 6644–6653 | date = December 2001 | pmid = 11714836 | doi = 10.4049/jimmunol.167.11.6644 | doi-access = free }} * {{cite journal | vauthors = Ebert LM, McColl SR | title = Up-regulation of CCR5 and CCR6 on distinct subpopulations of antigen-activated CD4+ T lymphocytes | journal = Journal of Immunology | volume = 168 | issue = 1 | pages = 65–72 | date = January 2002 | pmid = 11751947 | doi = 10.4049/jimmunol.168.1.65 | doi-access = free }} * {{cite journal | vauthors = Liao F, Shirakawa AK, Foley JF, Rabin RL, Farber JM | title = 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 = Journal of Immunology | volume = 168 | issue = 10 | pages = 4871–4880 | date = May 2002 | pmid = 11994436 | doi = 10.4049/jimmunol.168.10.4871 | doi-access = free }} * {{cite journal | vauthors = Hosokawa Y, Nakanishi T, Yamaguchi D, Takahashi K, Yumoto H, Ozaki K, Matsuo T | title = Macrophage inflammatory protein 3alpha-CC chemokine receptor 6 interactions play an important role in CD4+ T-cell accumulation in periodontal diseased tissue | journal = Clinical and Experimental Immunology | volume = 128 | issue = 3 | pages = 548–554 | date = June 2002 | pmid = 12067311 | pmc = 1906256 | doi = 10.1046/j.1365-2249.2002.01865.x }} * {{cite journal | vauthors = Kim CH, Johnston B, Butcher EC | title = 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 | journal = Blood | volume = 100 | issue = 1 | pages = 11–16 | date = July 2002 | pmid = 12070001 | doi = 10.1182/blood-2001-12-0196 | s2cid = 37076470 | doi-access = free }} * {{cite journal | vauthors = Ai LS, Liao F | title = Mutating the four extracellular cysteines in the chemokine receptor CCR6 reveals their differing roles in receptor trafficking, ligand binding, and signaling | journal = Biochemistry | volume = 41 | issue = 26 | pages = 8332–8341 | date = July 2002 | pmid = 12081481 | doi = 10.1021/bi025855y }} * {{cite journal | vauthors = Hoover DM, Boulegue C, Yang D, Oppenheim JJ, Tucker K, Lu W, Lubkowski J | title = The structure of human macrophage inflammatory protein-3alpha /CCL20. Linking antimicrobial and CC chemokine receptor-6-binding activities with human beta-defensins | journal = The Journal of Biological Chemistry | volume = 277 | issue = 40 | pages = 37647–37654 | date = October 2002 | pmid = 12149255 | doi = 10.1074/jbc.M203907200 | doi-access = free }} * {{cite journal | vauthors = Maki W, Morales RE, Carroll VA, Telford WG, Knibbs RN, Stoolman LM, Hwang ST | title = CCR6 colocalizes with CD18 and enhances adhesion to activated endothelial cells in CCR6-transduced Jurkat T cells | journal = Journal of Immunology | volume = 169 | issue = 5 | pages = 2346–2353 | date = September 2002 | pmid = 12193700 | doi = 10.4049/jimmunol.169.5.2346 | doi-access = free }} {{refend}}
{{NLM content}} {{Cytokine receptors}} {{Clusters of differentiation}} {{Chemokine receptor modulators}}
Category:Chemokine receptors Category:Clusters of differentiation