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Gene Review

CCR8  -  chemokine (C-C motif) receptor 8

Homo sapiens

Synonyms: C-C CKR-8, C-C chemokine receptor type 8, CC chemokine receptor CHEMR1, CC-CKR-8, CCR-8, ...
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Disease relevance of CCR8


High impact information on CCR8

  • Here we examine the role of an intermolecular hTER-hTER interaction in the previously reported functional dimerization of telomerase [5].
  • Here, we show that the majority of human T cells in healthy skin express the chemokine receptor CCR8 and respond to its selective ligand I-309/CCL1 [6].
  • Secretion of interleukin (IL)-4, IL-10, and transforming growth factor-beta was low to undetectable, arguing against a strict association of CCR8 expression with either T helper cell 2 or regulatory T cell subsets [6].
  • Characterization of Gr-1int monocytes revealed that they selectively expressed CCR7 and CCR8 mRNA in blood [7].
  • Role of CCR8 and other chemokine pathways in the migration of monocyte-derived dendritic cells to lymph nodes [7].

Chemical compound and disease context of CCR8

  • The aim of our study was to characterize the role of the CC chemokine receptor 8 (CCR8), the only described receptor for CCL1, in the rescue of murine thymic lymphoma cells and murine thymocytes from dexamethasone (dex)-induced apoptosis [8].
  • To determine the degree and potential importance of this effect, we measured the transcapillary escape rate (TER) of (125)I-labeled albumin in 12 adult patients fulfilling American College of Chest Physicians/Society of Critical Care Medicine criteria for septic shock [9].

Biological context of CCR8


Anatomical context of CCR8


Associations of CCR8 with chemical compounds

  • The C-C chemokine receptors CCR4 and CCR8 identify airway T cells of allergen-challenged atopic asthmatics [14].
  • We report here that vMIP-I binds to and induces cytosolic [Ca(2+)] signals in human T cells selectively through CCR8, a CC chemokine receptor associated with Th2 lymphocytes [17].
  • Here, we show that human peripheral blood CD4(+) and CD8(+) cutaneous (CLA(+)), but not intestinal memory (integrin beta(7) (+)) nor IL-4-producing T cells, represent major subpopulations of circulating T cells that specifically migrate in response to the chemokine I-309/CCL1 by virtue of CCR8 expression [18].
  • NH(2)-terminal extension of the mature CCL1 sequence by a serine residue (Ser-CCL1) resulted in a partial agonist with a reduced affinity for CCR8, suggesting that the NH(2) terminus of the ligand plays a role in ligand binding to an intrahelical site [19].
  • The design, synthesis, and structure-activity relationship development of naphthalene-derived human CCR8 antagonists is described [20].

Physical interactions of CCR8

  • Both I309 and vMIP-1 bind CCR8, strongly suggesting that this isolate can use CCR8 on primary cells [21].

Regulatory relationships of CCR8

  • To identify the ligand of CKR-L1, we have studied chemokine-induced calcium mobilization in 293 cells transfected with CKR-L1 [1].
  • No point mutants, except GUN-1/L, grew well in NP-2/CD4 cells expressing CCR8 [22].
  • Similarly, vMIP-I responses were more than 2 orders of magnitude more sensitive to the specific CCR8 antagonist MC148 than those induced by CCL1, which is difficult to reconcile with the reported affinities for the receptor [19].
  • These cells were 44.7% (32.6% to 50.0%) IL-4(+) and only 2.5% (0.6% to 3.3%) IFN-(gamma) and showed a greater than 5-fold upregulation of CCR4 expression to 54.0% (40.7% to 67.8%) after culture, whereas CCR3 was expressed on 9.7% (7.4% to 18.9%) of allergen-reactive cells and CCR8 on less than 1% [23].

Other interactions of CCR8


Analytical, diagnostic and therapeutic context of CCR8


  1. Identification of CCR8 as the specific receptor for the human beta-chemokine I-309: cloning and molecular characterization of murine CCR8 as the receptor for TCA-3. Goya, I., Gutiérrez, J., Varona, R., Kremer, L., Zaballos, A., Márquez, G. J. Immunol. (1998) [Pubmed]
  2. The CC chemokine I-309 inhibits CCR8-dependent infection by diverse HIV-1 strains. Horuk, R., Hesselgesser, J., Zhou, Y., Faulds, D., Halks-Miller, M., Harvey, S., Taub, D., Samson, M., Parmentier, M., Rucker, J., Doranz, B.J., Doms, R.W. J. Biol. Chem. (1998) [Pubmed]
  3. Utilization of chemokine receptors, orphan receptors, and herpesvirus-encoded receptors by diverse human and simian immunodeficiency viruses. Rucker, J., Edinger, A.L., Sharron, M., Samson, M., Lee, B., Berson, J.F., Yi, Y., Margulies, B., Collman, R.G., Doranz, B.J., Parmentier, M., Doms, R.W. J. Virol. (1997) [Pubmed]
  4. The chemokine receptor CCR8 mediates human endothelial cell chemotaxis induced by I-309 and Kaposi sarcoma herpesvirus-encoded vMIP-I and by lipoprotein(a)-stimulated endothelial cell conditioned medium. Haque, N.S., Fallon, J.T., Taubman, M.B., Harpel, P.C. Blood (2001) [Pubmed]
  5. A role for a novel 'trans-pseudoknot' RNA-RNA interaction in the functional dimerization of human telomerase. Ly, H., Xu, L., Rivera, M.A., Parslow, T.G., Blackburn, E.H. Genes Dev. (2003) [Pubmed]
  6. A skin-selective homing mechanism for human immune surveillance T cells. Schaerli, P., Ebert, L., Willimann, K., Blaser, A., Roos, R.S., Loetscher, P., Moser, B. J. Exp. Med. (2004) [Pubmed]
  7. Role of CCR8 and other chemokine pathways in the migration of monocyte-derived dendritic cells to lymph nodes. Qu, C., Edwards, E.W., Tacke, F., Angeli, V., Llodrá, J., Sanchez-Schmitz, G., Garin, A., Haque, N.S., Peters, W., van Rooijen, N., Sanchez-Torres, C., Bromberg, J., Charo, I.F., Jung, S., Lira, S.A., Randolph, G.J. J. Exp. Med. (2004) [Pubmed]
  8. The chemokine receptor CCR8 mediates rescue from dexamethasone-induced apoptosis via an ERK-dependent pathway. Spinetti, G., Bernardini, G., Camarda, G., Mangoni, A., Santoni, A., Capogrossi, M.C., Napolitano, M. J. Leukoc. Biol. (2003) [Pubmed]
  9. Effects of albumin supplementation on microvascular permeability in septic patients. Margarson, M.P., Soni, N.C. J. Appl. Physiol. (2002) [Pubmed]
  10. Identification of CCR8: a human monocyte and thymus receptor for the CC chemokine I-309. Tiffany, H.L., Lautens, L.L., Gao, J.L., Pease, J., Locati, M., Combadiere, C., Modi, W., Bonner, T.I., Murphy, P.M. J. Exp. Med. (1997) [Pubmed]
  11. Unique chemotactic response profile and specific expression of chemokine receptors CCR4 and CCR8 by CD4(+)CD25(+) regulatory T cells. Iellem, A., Mariani, M., Lang, R., Recalde, H., Panina-Bordignon, P., Sinigaglia, F., D'Ambrosio, D. J. Exp. Med. (2001) [Pubmed]
  12. LEC induces chemotaxis and adhesion by interacting with CCR1 and CCR8. Howard, O.M., Dong, H.F., Shirakawa, A.K., Oppenheim, J.J. Blood (2000) [Pubmed]
  13. Chemokine receptor expression and function in CD4+ T lymphocytes with regulatory activity. Sebastiani, S., Allavena, P., Albanesi, C., Nasorri, F., Bianchi, G., Traidl, C., Sozzani, S., Girolomoni, G., Cavani, A. J. Immunol. (2001) [Pubmed]
  14. The C-C chemokine receptors CCR4 and CCR8 identify airway T cells of allergen-challenged atopic asthmatics. Panina-Bordignon, P., Papi, A., Mariani, M., Di Lucia, P., Casoni, G., Bellettato, C., Buonsanti, C., Miotto, D., Mapp, C., Villa, A., Arrigoni, G., Fabbri, L.M., Sinigaglia, F. J. Clin. Invest. (2001) [Pubmed]
  15. Chemokine receptor-8 (CCR8) mediates human vascular smooth muscle cell chemotaxis and metalloproteinase-2 secretion. Haque, N.S., Fallon, J.T., Pan, J.J., Taubman, M.B., Harpel, P.C. Blood (2004) [Pubmed]
  16. Human NK cells express CC chemokine receptors 4 and 8 and respond to thymus and activation-regulated chemokine, macrophage-derived chemokine, and I-309. Inngjerdingen, M., Damaj, B., Maghazachi, A.A. J. Immunol. (2000) [Pubmed]
  17. HHV8-encoded vMIP-I selectively engages chemokine receptor CCR8. Agonist and antagonist profiles of viral chemokines. Dairaghi, D.J., Fan, R.A., McMaster, B.E., Hanley, M.R., Schall, T.J. J. Biol. Chem. (1999) [Pubmed]
  18. Skin-homing CLA+ T cells and regulatory CD25+ T cells represent major subsets of human peripheral blood memory T cells migrating in response to CCL1/I-309. Colantonio, L., Iellem, A., Sinigaglia, F., D'Ambrosio, D. Eur. J. Immunol. (2002) [Pubmed]
  19. Structure/Function Relationships of CCR8 Agonists and Antagonists: AMINO-TERMINAL EXTENSION OF CCL1 BY A SINGLE AMINO ACID GENERATES A PARTIAL AGONIST. Fox, J.M., Najarro, P., Smith, G.L., Struyf, S., Proost, P., Pease, J.E. J. Biol. Chem. (2006) [Pubmed]
  20. Design, Synthesis, and Evaluation of Naphthalene-Sulfonamide Antagonists of Human CCR8. Jenkins, T.J., Guan, B., Dai, M., Li, G., Lightburn, T.E., Huang, S., Freeze, B.S., Burdi, D.F., Jacutin-Porte, S., Bennett, R., Chen, W., Minor, C., Ghosh, S., Blackburn, C., Gigstad, K.M., Jones, M., Kolbeck, R., Yin, W., Smith, S., Cardillo, D., Ocain, T.D., Harriman, G.C. J. Med. Chem. (2007) [Pubmed]
  21. Use of alternate coreceptors on primary cells by two HIV-1 isolates. Cilliers, T., Willey, S., Sullivan, W.M., Patience, T., Pugach, P., Coetzer, M., Papathanasopoulos, M., Moore, J.P., Trkola, A., Clapham, P., Morris, L. Virology (2005) [Pubmed]
  22. Changes in and discrepancies between cell tropisms and coreceptor uses of human immunodeficiency virus type 1 induced by single point mutations at the V3 tip of the env protein. Shimizu, N., Haraguchi, Y., Takeuchi, Y., Soda, Y., Kanbe, K., Hoshino, H. Virology (1999) [Pubmed]
  23. Adenoid-derived TH2 cells reactive to allergen and recall antigen express CC chemokine receptor 4. Banwell, M.E., Robinson, D.S., Lloyd, C.M. J. Allergy Clin. Immunol. (2003) [Pubmed]
  24. Release of both CCR4-active and CXCR3-active chemokines during human allergic pulmonary late-phase reactions. Bochner, B.S., Hudson, S.A., Xiao, H.Q., Liu, M.C. J. Allergy Clin. Immunol. (2003) [Pubmed]
  25. 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]
  26. Molecular cloning of TER1, a chemokine receptor-like gene expressed by lymphoid tissues. Napolitano, M., Zingoni, A., Bernardini, G., Spinetti, G., Nista, A., Storlazzi, C.T., Rocchi, M., Santoni, A. J. Immunol. (1996) [Pubmed]
  27. Identification of CCR8, the receptor for the human CC chemokine I-309. Roos, R.S., Loetscher, M., Legler, D.F., Clark-Lewis, I., Baggiolini, M., Moser, B. J. Biol. Chem. (1997) [Pubmed]
  28. Expression of chemokines and chemokine receptors during human renal transplant rejection. Segerer, S., Cui, Y., Eitner, F., Goodpaster, T., Hudkins, K.L., Mack, M., Cartron, J.P., Colin, Y., Schlondorff, D., Alpers, C.E. Am. J. Kidney Dis. (2001) [Pubmed]
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