The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Ccr4  -  chemokine (C-C motif) receptor 4

Mus musculus

Synonyms: C-C CKR-4, C-C chemokine receptor type 4, CC CKR-4, CC-CKR-4, CCR-4, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Ccr4


High impact information on Ccr4

  • Here we show that Cnot7(-/-) males are sterile owing to oligo-astheno-teratozoospermia, suggesting that Cnot7, a CCR4-associated transcriptional cofactor, is essential for spermatogenesis [6].
  • A cofactor required for infection with virus adapted for growth in transformed T-cell lines was recently identified and named fusin [7].
  • Recruitment of Foxp3+ T regulatory cells mediating allograft tolerance depends on the CCR4 chemokine receptor [8].
  • Expression of the chemokine receptor CCR4 is strongly associated with trafficking of specialized cutaneous memory T helper (Th) lymphocytes to the skin [9].
  • We have addressed this issue via competitive bone marrow (BM) reconstitution assays; equal numbers of BM cells from CCR4(+/+) and CCR4(-/-) donors were allowed to develop side-by-side within RAG-1(-/-) hosts [9].

Chemical compound and disease context of Ccr4

  • Systemic immunoneutralization of CCL22 from the time of egg injection into S. mansoni-sensitized mice for 8 days significantly decreased CCR4 protein expression, the eosinophil content, the overall size of the egg granuloma, and its hydroxyproline content [10].

Biological context of Ccr4

  • Amino acid sequence comparison shows that CHEMR1 is 84% identical to human CCR-4, indicating that CHEMR1 is likely to be a mouse CCR-4 [11].
  • Splenocytes and thymocytes isolated from the CCR4(-/-) mice failed to respond to the CCR4 ligands TARC and MDC, as expected, but also surprisingly did not undergo chemotaxis in vitro in response to macrophage inflammatory protein (MIP)-1alpha [12].
  • CCR4-deficient mice show prolonged graft survival in a chronic cardiac transplant rejection model [13].
  • These findings indicate that CCR4 is involved in the recruitment of NK1.1(+)CD3(+) cells into cardiac allografts and clearly establish an important and novel role for CCR4 in chronic graft rejection [13].
  • Furthermore, expression of CCR4 and CCR5, two chemokine receptors implicated in cell adhesion, was found to be downregulated 16 h after infection (2.8 to 4.1 times and 1.9 to 2.8 times, respectively) [14].

Anatomical context of Ccr4

  • This may reflect a defect in the ability of the CCR4(-/-) macrophages to be retained in the peritoneal cavity [12].
  • Cumulatively, the results demonstrate that CCR4-bearing T cells participate in the development of such tissue-driven autoimmune reactions [2].
  • Astrocytes contain mRNA for CCR1, but messages for CCR4 and the orphan chemokine receptor MIP-1alphaR-like#1 were not detected [15].
  • Positively selected CD69+CD3intermediate cells gained CCR4, of which ligand, thymus activation-regulated chemokine, was expressed in the medulla [16].
  • In brain, however, TCR vaccination did not produce significant changes in chemokine expression but resulted in an increased expression of CCR3 and CCR4 usually associated with Th2 cells [17].

Associations of Ccr4 with chemical compounds

  • However, CCR4(-/-) mice exhibited significantly decreased mortality on administration of high or low dose bacterial lipopolysaccharide (LPS) compared with CCR4(+/+) mice [12].
  • In contrast, in a gallium nitrate chronic cardiac allograft rejection model, cardiac graft survival was significantly prolonged in CCR4(-/-) recipients [13].
  • Significant airway hyperresponsiveness to intravenous methacholine was observed at day 3 in CCR4-/- mice, whereas at days 7 and 30, airway hyperresponsiveness was attenuated in these mice compared with control mice [4].

Other interactions of Ccr4

  • Targeting CLA/E-selectin interactions prevents CCR4-mediated recruitment of human Th2 memory cells to human skin in vivo [1].
  • Recent studies have shown that CCR4 is the major chemokine receptor expressed by T helper type 2 (Th2) polarized cells [12].
  • Cells expressing the CCR4 ligand TARC (thymus- and activation-regulated chemokine) were detected within infiltrated islets from prediabetic mice [2].
  • CCR4 and CCR8 agonists are also likely contributors [18].
  • In uninfected mice, IL-4-producing T cells preferentially migrated to the CCR4 ligand, CCL17, whereas IFN-gamma-expressing T cells as well as populations of IL-4+ or IL-10+ T cells migrated to the CXCR3 ligand, CXCL9 [19].

Analytical, diagnostic and therapeutic context of Ccr4


  1. Targeting CLA/E-selectin interactions prevents CCR4-mediated recruitment of human Th2 memory cells to human skin in vivo. Biedermann, T., Schwärzler, C., Lametschwandtner, G., Thoma, G., Carballido-Perrig, N., Kund, J., de Vries, J.E., Rot, A., Carballido, J.M. Eur. J. Immunol. (2002) [Pubmed]
  2. CCR4-bearing T cells participate in autoimmune diabetes. Kim, S.H., Cleary, M.M., Fox, H.S., Chantry, D., Sarvetnick, N. J. Clin. Invest. (2002) [Pubmed]
  3. Immunosuppressive effects of CCL17 on pulmonary antifungal responses during pulmonary invasive aspergillosis. Carpenter, K.J., Hogaboam, C.M. Infect. Immun. (2005) [Pubmed]
  4. Airway hyperresponsiveness, but not airway remodeling, is attenuated during chronic pulmonary allergic responses to Aspergillus in CCR4-/- mice. Schuh, J.M., Power, C.A., Proudfoot, A.E., Kunkel, S.L., Lukacs, N.W., Hogaboam, C.M. FASEB J. (2002) [Pubmed]
  5. CC chemokine receptor (CCR)4 and the CCR10 ligand cutaneous T cell-attracting chemokine (CTACK) in lymphocyte trafficking to inflamed skin. Reiss, Y., Proudfoot, A.E., Power, C.A., Campbell, J.J., Butcher, E.C. J. Exp. Med. (2001) [Pubmed]
  6. Oligo-astheno-teratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta. Nakamura, T., Yao, R., Ogawa, T., Suzuki, T., Ito, C., Tsunekawa, N., Inoue, K., Ajima, R., Miyasaka, T., Yoshida, Y., Ogura, A., Toshimori, K., Noce, T., Yamamoto, T., Noda, T. Nat. Genet. (2004) [Pubmed]
  7. Identification of a major co-receptor for primary isolates of HIV-1. Deng, H., Liu, R., Ellmeier, W., Choe, S., Unutmaz, D., Burkhart, M., Di Marzio, P., Marmon, S., Sutton, R.E., Hill, C.M., Davis, C.B., Peiper, S.C., Schall, T.J., Littman, D.R., Landau, N.R. Nature (1996) [Pubmed]
  8. Recruitment of Foxp3+ T regulatory cells mediating allograft tolerance depends on the CCR4 chemokine receptor. Lee, I., Wang, L., Wells, A.D., Dorf, M.E., Ozkaynak, E., Hancock, W.W. J. Exp. Med. (2005) [Pubmed]
  9. A role for CCR4 in development of mature circulating cutaneous T helper memory cell populations. Baekkevold, E.S., Wurbel, M.A., Kivisäkk, P., Wain, C.M., Power, C.A., Haraldsen, G., Campbell, J.J. J. Exp. Med. (2005) [Pubmed]
  10. Role of CCR4 ligands, CCL17 and CCL22, during Schistosoma mansoni egg-induced pulmonary granuloma formation in mice. Jakubzick, C., Wen, H., Matsukawa, A., Keller, M., Kunkel, S.L., Hogaboam, C.M. Am. J. Pathol. (2004) [Pubmed]
  11. Molecular cloning and characterization of a cDNA, CHEMR1, encoding a chemokine receptor with a homology to the human C-C chemokine receptor, CCR-4. Youn, B.S., Kim, S.H., Lyu, M.S., Kozak, C.A., Taub, D.D., Kwon, B.S. Blood (1997) [Pubmed]
  12. A key role for CC chemokine receptor 4 in lipopolysaccharide-induced endotoxic shock. Chvatchko, Y., Hoogewerf, A.J., Meyer, A., Alouani, S., Juillard, P., Buser, R., Conquet, F., Proudfoot, A.E., Wells, T.N., Power, C.A. J. Exp. Med. (2000) [Pubmed]
  13. CCR4-deficient mice show prolonged graft survival in a chronic cardiac transplant rejection model. Hüser, N., Tertilt, C., Gerauer, K., Maier, S., Traeger, T., Assfalg, V., Reiter, R., Heidecke, C.D., Pfeffer, K. Eur. J. Immunol. (2005) [Pubmed]
  14. Leishmania infection impairs beta 1-integrin function and chemokine receptor expression in mononuclear phagocytes. Pinheiro, N.F., Hermida, M.D., Macedo, M.P., Mengel, J., Bafica, A., dos-Santos, W.L. Infect. Immun. (2006) [Pubmed]
  15. Murine astrocytes express a functional chemokine receptor. Tanabe, S., Heesen, M., Berman, M.A., Fischer, M.B., Yoshizawa, I., Luo, Y., Dorf, M.E. J. Neurosci. (1997) [Pubmed]
  16. Pertussis toxin-sensitive signal controls the trafficking of thymocytes across the corticomedullary junction in the thymus. Suzuki, G., Sawa, H., Kobayashi, Y., Nakata, Y., Nakagawa, K., Uzawa, A., Sakiyama, H., Kakinuma, S., Iwabuchi, K., Nagashima, K. J. Immunol. (1999) [Pubmed]
  17. Reduced chemokine and chemokine receptor expression in spinal cords of TCR BV8S2 transgenic mice protected against experimental autoimmune encephalomyelitis with BV8S2 protein. Matejuk, A., Vandenbark, A.A., Burrows, G.G., Bebo, B.F., Offner, H. J. Immunol. (2000) [Pubmed]
  18. Chemokine responses in schistosomal antigen-elicited granuloma formation. Chiu, B.C., Chensue, S.W. Parasite Immunol. (2002) [Pubmed]
  19. Chemotactic responses of IL-4-, IL-10-, and IFN-gamma-producing CD4+ T cells depend on tissue origin and microbial stimulus. Debes, G.F., Dahl, M.E., Mahiny, A.J., Bonhagen, K., Campbell, D.J., Siegmund, K., Erb, K.J., Lewis, D.B., Kamradt, T., Hamann, A. J. Immunol. (2006) [Pubmed]
  20. Induction of macrophage-derived chemokine/CCL22 expression in experimental autoimmune encephalomyelitis and cultured microglia: implications for disease regulation. Columba-Cabezas, S., Serafini, B., Ambrosini, E., Sanchez, M., Penna, G., Adorini, L., Aloisi, F. J. Neuroimmunol. (2002) [Pubmed]
WikiGenes - Universities