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Gene Review

CCR6  -  chemokine (C-C motif) receptor 6

Homo sapiens

Synonyms: BN-1, C-C CKR-6, C-C chemokine receptor type 6, CC-CKR-6, CCR-6, ...
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Disease relevance of CCR6


High impact information on CCR6

  • Beta-defensins interact with CCR6; murine beta-defensin-2 in addition activates TLR4 [5].
  • Human beta-defensin was selectively chemotactic for cells stably transfected to express human CCR6, a chemokine receptor preferentially expressed by immature dendritic cells and memory T cells [3].
  • Thus, beta-defensins may promote adaptive immune responses by recruiting dendritic and T cells to the site of microbial invasion through interaction with CCR6 [3].
  • These immediate precursors expressed CD14, langerin and functional CCR6 [6].
  • Immunohistochemical analysis on 13 LCH biopsies of bone, skin, and lymph node all expressed the immature dendritic cell (DC) marker CCR6 on the lesional LCs and absence of the mature DC marker CCR7 [7].

Biological context of CCR6

  • Up-regulation of CCR5 and CCR6 on distinct subpopulations of antigen-activated CD4+ T lymphocytes [8].
  • The observed increase in expression correlated well with the acquisition of an activated/memory phenotype and was largely (CCR5) or completely (CCR6) separated temporally from the initiation of cell division [8].
  • Of particular interest is the fact that the enhanced activity on B cells was not associated with an increase in CCR6 expression as assessed by levels of receptor mRNA, surface staining, or MIP-3alpha/CCL20 binding sites, or by a change in the affinity of the receptor for ligand [9].
  • In this review, the discovery, the gene and protein structure, the in vitro biological activities, the cell and inducer specific expression and the tissue distribution of CCL20 and CCR6 are discussed [10].
  • These data convincingly demonstrate that responses to a chemokine can be regulated solely by changes in the downstream pathways for signal transduction resulting from Ag receptor activation, and establish CCR6 as an efficacious receptor on human B cells [9].

Anatomical context of CCR6

  • Expression of CCR6 by pathologic LCs may contribute to their accumulation in nonlymphoid organs such as skin and bone, whereas CCR7 expression may direct them to lymphoid tissue [1].
  • Moreover, skin-homing CLA+ memory T cells express high levels of surface CCR6 [11].
  • We have shown previously that CCR6 is expressed on peripheral blood B cells, but CCR6 activity on these cells is low in in vitro assays [9].
  • The ligand-receptor pair CCL20-CCR6 is responsible for the chemoattraction of immature dendritic cells (DC), effector/memory T-cells and B-cells and plays a role at skin and mucosal surfaces under homeostatic and inflammatory conditions, as well as in pathology, including cancer and rheumatoid arthritis [10].
  • Immunohistochemical examination of cryosections of term placental villous tissue confirmed the expression of CCR3, CXCR4, and CCR6 by trophoblast cells [12].

Associations of CCR6 with chemical compounds


Physical interactions of CCR6

  • BACKGROUND: Human CC chemokine Macrophage Inflammatory Protein-3alpha (MIP-3alpha) directs inflammatory cell migration through its binding to the transmembrane receptor CCR6 [17].

Regulatory relationships of CCR6

  • LARC induced migration in 293/EBNA-1 cells stably expressing GPR-CY4 with a bi-modal dose-response curve [18].
  • CCR6(+) CD8(+) T cells express granzyme A and a low level of perforin but not granzyme B [19].
  • Among recombinant cytokines, TNF-alpha induced high levels of CCR6 mRNA expression, whereas interferon (IFN)-gamma induced low levels [13].
  • None of the CD34(+)Lin(-) hematopoietic stem cell progenitors or the CD34(+)CD19(+) (pro-B) or the CD19(+)CD10(+) (pre-B/immature B cells) B-cell progenitors expressed CCR6 [20].
  • In contrast, IFN-gamma-induced CCR6 loss was irreversible and was concomitant to the induction of DC maturation [21].

Other interactions of CCR6

  • Taken together, these findings strongly suggest that CCL20/CCR6 may play a role in the recruitment of T cells to lesional psoriatic skin [11].
  • The acquisition of inflammatory chemokine receptors, such as CCR5 and CCR6, may contribute to the efficient relocation of activated T cells to inflamed sites in the periphery [8].
  • CC chemokine receptor (CCR) 1 to CCR6 were up-regulated after culture [22].
  • The cell surface expression of the chemokine receptors CXCR5 and CCR6 was decreased in SLE patients compared with controls (P = 0.051 and P = 0.002, respectively) [23].
  • The reduced CCR6 and CXCR3 expression on PBL correlated with the reduced memory phenotype in circulation and increased memory phenotype in liver [24].

Analytical, diagnostic and therapeutic context of CCR6


  1. Coincident expression of the chemokine receptors CCR6 and CCR7 by pathologic Langerhans cells in Langerhans cell histiocytosis. Fleming, M.D., Pinkus, J.L., Fournier, M.V., Alexander, S.W., Tam, C., Loda, M., Sallan, S.E., Nichols, K.E., Carpentieri, D.F., Pinkus, G.S., Rollins, B.J. Blood (2003) [Pubmed]
  2. Involvement of Chemokine Receptor CCR6 in Colorectal Cancer Metastasis. Rubie, C., Oliveira, V., Kempf, K., Wagner, M., Tilton, B., Rau, B., Kruse, B., Konig, J., Schilling, M. Tumour Biol. (2006) [Pubmed]
  3. Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Yang, D., Chertov, O., Bykovskaia, S.N., Chen, Q., Buffo, M.J., Shogan, J., Anderson, M., Schröder, J.M., Wang, J.M., Howard, O.M., Oppenheim, J.J. Science (1999) [Pubmed]
  4. Detection and localization of Mip-3alpha/LARC/Exodus, a macrophage proinflammatory chemokine, and its CCR6 receptor in human pancreatic cancer. Kleeff, J., Kusama, T., Rossi, D.L., Ishiwata, T., Maruyama, H., Friess, H., Büchler, M.W., Zlotnik, A., Korc, M. Int. J. Cancer (1999) [Pubmed]
  5. Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense. Yang, D., Biragyn, A., Hoover, D.M., Lubkowski, J., Oppenheim, J.J. Annu. Rev. Immunol. (2004) [Pubmed]
  6. Dermal-resident CD14+ cells differentiate into Langerhans cells. Larregina, A.T., Morelli, A.E., Spencer, L.A., Logar, A.J., Watkins, S.C., Thomson, A.W., Falo, L.D. Nat. Immunol. (2001) [Pubmed]
  7. Aberrant chemokine receptor expression and chemokine production by Langerhans cells underlies the pathogenesis of Langerhans cell histiocytosis. Annels, N.E., Da Costa, C.E., Prins, F.A., Willemze, A., Hogendoorn, P.C., Egeler, R.M. J. Exp. Med. (2003) [Pubmed]
  8. Up-regulation of CCR5 and CCR6 on distinct subpopulations of antigen-activated CD4+ T lymphocytes. Ebert, L.M., McColl, S.R. J. Immunol. (2002) [Pubmed]
  9. 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. Liao, F., Shirakawa, A.K., Foley, J.F., Rabin, R.L., Farber, J.M. J. Immunol. (2002) [Pubmed]
  10. The CC chemokine CCL20 and its receptor CCR6. Schutyser, E., Struyf, S., Van Damme, J. Cytokine Growth Factor Rev. (2003) [Pubmed]
  11. Up-regulation of macrophage inflammatory protein-3 alpha/CCL20 and CC chemokine receptor 6 in psoriasis. Homey, B., Dieu-Nosjean, M.C., Wiesenborn, A., Massacrier, C., Pin, J.J., Oldham, E., Catron, D., Buchanan, M.E., Müller, A., deWaal Malefyt, R., Deng, G., Orozco, R., Ruzicka, T., Lehmann, P., Lebecque, S., Caux, C., Zlotnik, A. J. Immunol. (2000) [Pubmed]
  12. Chemokine receptor expression by human syncytiotrophoblast. Douglas, G.C., Thirkill, T.L., Sideris, V., Rabieh, M., Trollinger, D., Nuccitelli, R. J. Reprod. Immunol. (2001) [Pubmed]
  13. Expression of CCR6 and CD83 by cytokine-activated human neutrophils. Yamashiro, S., Wang, J.M., Yang, D., Gong, W.H., Kamohara, H., Yoshimura, T. Blood (2000) [Pubmed]
  14. Mutating the four extracellular cysteines in the chemokine receptor CCR6 reveals their differing roles in receptor trafficking, ligand binding, and signaling. Ai, L.S., Liao, F. Biochemistry (2002) [Pubmed]
  15. Chemokine CCL20 enhances the growth of HuH7 cells via phosphorylation of p44/42 MAPK in vitro. Fujii, H., Itoh, Y., Yamaguchi, K., Yamauchi, N., Harano, Y., Nakajima, T., Minami, M., Okanoue, T. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  16. An abnormal mitochondrial-hypoxia inducible factor-1alpha-Kv channel pathway disrupts oxygen sensing and triggers pulmonary arterial hypertension in fawn hooded rats: similarities to human pulmonary arterial hypertension. Bonnet, S., Michelakis, E.D., Porter, C.J., Andrade-Navarro, M.A., Thébaud, B., Bonnet, S., Haromy, A., Harry, G., Moudgil, R., McMurtry, M.S., Weir, E.K., Archer, S.L. Circulation (2006) [Pubmed]
  17. Macrophage inflammatory protein-3alpha promotes pancreatic cancer cell invasion. Campbell, A.S., Albo, D., Kimsey, T.F., White, S.L., Wang, T.N. J. Surg. Res. (2005) [Pubmed]
  18. Identification of CCR6, the specific receptor for a novel lymphocyte-directed CC chemokine LARC. Baba, M., Imai, T., Nishimura, M., Kakizaki, M., Takagi, S., Hieshima, K., Nomiyama, H., Yoshie, O. J. Biol. Chem. (1997) [Pubmed]
  19. Functional expression of chemokine receptor CCR6 on human effector memory CD8(+) T cells. Kondo, T., Takata, H., Takiguchi, M. Eur. J. Immunol. (2007) [Pubmed]
  20. Regulation of CCR6 chemokine receptor expression and responsiveness to macrophage inflammatory protein-3alpha/CCL20 in human B cells. Krzysiek, R., Lefevre, E.A., Bernard, J., Foussat, A., Galanaud, P., Louache, F., Richard, Y. Blood (2000) [Pubmed]
  21. IL-10 induces CCR6 expression during Langerhans cell development while IL-4 and IFN-gamma suppress it. Dieu-Nosjean, M.C., Massacrier, C., Vanbervliet, B., Fridman, W.H., Caux, C. J. Immunol. (2001) [Pubmed]
  22. Chemotaxis of human tonsil B lymphocytes to CC chemokine receptor (CCR) 1, CCR2 and CCR4 ligands is restricted to non-germinal center cells. Corcione, A., Tortolina, G., Bonecchi, R., Battilana, N., Taborelli, G., Malavasi, F., Sozzani, S., Ottonello, L., Dallegri, F., Pistoia, V. Int. Immunol. (2002) [Pubmed]
  23. Abnormal expression of chemokine receptors on T-cells from patients with systemic lupus erythematosus. Eriksson, C., Eneslätt, K., Ivanoff, J., Rantapää-Dahlqvist, S., Sundqvist, K.G. Lupus (2003) [Pubmed]
  24. Reduced expression of chemokine receptors on peripheral blood lymphocytes in patients with hepatocellular carcinoma. Liu, Y., Poon, R.T., Feng, X., Yu, W.C., Luk, J.M., Fan, S.T. Am. J. Gastroenterol. (2004) [Pubmed]
  25. In situ leukemic plasmacytoid dendritic cells pattern of chemokine receptors expression and in vitro migratory response. Bendriss-Vermare, N., Chaperot, L., Peoc'h, M., Vanbervliet, B., Jacob, M.C., Briere, F., Bensa, J.C., Caux, C., Plumas, J. Leukemia (2004) [Pubmed]
  26. MIP-3alpha/CCL20 in renal transplantation and its possible involvement as dendritic cell chemoattractant in allograft rejection. Woltman, A.M., de Fijter, J.W., van der Kooij, S.W., Jie, K.E., Massacrier, C., Caux, C., Daha, M.R., van Kooten, C. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. (2005) [Pubmed]
  27. CC Chemokine Receptor 6 Expression by B Lymphocytes Is Essential for the Development of Isolated Lymphoid Follicles. McDonald, K.G., McDonough, J.S., Wang, C., Kucharzik, T., Williams, I.R., Newberry, R.D. Am. J. Pathol. (2007) [Pubmed]
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