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Gene Review

Ccr5  -  chemokine (C-C motif) receptor 5

Mus musculus

Synonyms: AM4-7, C-C CKR-5, C-C chemokine receptor type 5, CC-CKR-5, CCR-5, ...
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Disease relevance of Ccr5

  • Collectively, the absence of CCR5 expression significantly impacts the ability of the host to control genital HSV-2 infection, inflammation, and spread associated with a specific reduction in NK cell expansion, infiltration, and activity in the nervous system [1].
  • These results indicate that the early stages of plaque formation in this model of lipid-mediated atherogenesis do not depend on CCR5 [2].
  • Chemokine receptor CCR5 deficiency exacerbates cerulein-induced acute pancreatitis in mice [3].
  • Moreover, individuals who are naturally deficient in CCR5 were reported to be at reduced risk for severe coronary artery disease (CAD) and early myocardial infarction (MI) [2].
  • CCR5(-/-) mice developed a more severe pancreatic injury than WT mice during cerulein-induced AP, as assessed by a more pronounced increase in serum amylase and lipase levels and by more severe pancreatic edema, inflammatory infiltrates (mainly neutrophils), and necrosis [3].

Psychiatry related information on Ccr5

  • Although mRNAs for the chemokine receptor CCR5, the lysosomal protease cathepsin S, and the pleiotropic cytokine transforming growth factor beta1 (TGF-beta1) were progressively upregulated in rodent CJD, the temporal patterns and peak magnitudes of each of these transcripts varied substantially among models [4].

High impact information on Ccr5

  • The protective effect of Ccl5 requires activation of the Ccr5 chemokine receptor and consequent bilateral activation of G(alphai)-PI3K-AKT and G(alphai)-MEK-ERK signaling pathways [5].
  • CCR5- and CXCR4-tropic HIV-1 are equally cytopathic for their T-cell targets in human lymphoid tissue [6].
  • Our results suggest that CCR5(+) apoptotic leukocytes act as 'terminators' of chemokine signaling during the resolution of inflammation [7].
  • CCR5 expression on apoptotic neutrophils and activated apoptotic T cells sequestered and effectively cleared CCL3 and CCL5 from sites of inflammation [7].
  • Here we report that during the resolution of peritonitis, the CCR5 chemokine receptor ligands CCL3 and CCL5 persisted in CCR5-deficient mice [7].

Chemical compound and disease context of Ccr5


Biological context of Ccr5


Anatomical context of Ccr5

  • Carotid artery allografts from Ccr5-deficient recipients showed better tissue preservation, and significant reduction of neointima formation and CD3+ T cell infiltration [17].
  • In conclusion, these in vivo data demonstrate that Ccr1, Ccr2, and Ccr5 mediate the postischemic recruitment of neutrophils through effects on intravascular adherence and subsequent transmigration [18].
  • Although, like Mecsas et al., we did not see any difference in the survival of the two groups of mice, we did find that there was a significantly reduced uptake of Y. pestis by Ccr5-deficient macrophages in vitro [13].
  • Fluorescence-activated cell sorter analysis of single-cell suspensions from obstructed kidneys revealed a prominent expression of CCR2 and CCR5 by infiltrating macrophages, whereas most lymphocytes expressed CCR5 only [19].
  • In addition, antibody-mediated depletion of NK cells resulted in an increase in HSV-2 levels in the vaginal, spinal cord, and brain stem tissue of wild-type but not CCR5(-/-) mice [1].

Associations of Ccr5 with chemical compounds

  • Furthermore, FTY720 administration uncovers a requirement for CXCR4 ligands for LN homing, but not for thymic egress, and CCR5 for thymic egress, but not LN homing [20].
  • Reduced IFN-gamma responses following PMA and ionomycin were also observed in CD8+ T cells of CCR5-/- and CCR2-/- mice [21].
  • The chemokine receptor CCR5 is not a necessary inflammatory mediator in kainic acid-induced hippocampal injury: evidence for a compensatory effect by increased CCR2 and CCR3 [22].
  • Interestingly, elevated expression of CCR1 and CCR5 by lymph node cells was also inhibited in 17 beta-estradiol treated mice with EAE [23].
  • TAK-779 is an antagonist for the chemokine receptors CCR5 and CXCR3, which are expressed on leukocytes, especially T-helper 1 cells, and these receptors may be involved in recruitment of these cells to atherosclerotic plaques [8].

Co-localisations of Ccr5


Regulatory relationships of Ccr5

  • Their migration to the CCR5 ligand MIP-1beta (CCL4) and homing to kidneys of Flt3L-treated recipients were inhibited by CCR5 antagonism [25].
  • Macrophage invasion was significantly impaired in CCR2-knockout mice when compared with wildtype controls and CCR5-deficient mice [26].
  • These results suggest that MIP-1alpha-induced migration of CCR5-expressing CD8(+) T cells into the portal areas of the liver plays a significant role in causing liver injury in GVHD; thus, CCR5 and its ligand may be the novel target molecules of therapeutic intervention of hepatic GVHD [27].
  • CC chemokine receptor 5 (CCR5) is expressed preferentially by CD4(+) T helper 1 (Th1) cells [28].
  • In this study, we demonstrate that CCR5 deficiency promotes the development of acute FLF in mice following Con A administration by preventing activated hepatic CD1d-restricted NKT cells (but not conventional T cells) from dying from activation-induced apoptosis [29].

Other interactions of Ccr5

  • Deficiency in CCR5 but not CCR1 protects against neointima formation in atherosclerosis-prone mice: involvement of IL-10 [30].
  • Depletion of gamma delta T cells reduced expression of CCR1 and CCR5 at disease onset only [31].
  • To the contrary, during the late phase of infection, an exaggerated Ag-specific IFN-gamma response was evident in CCR5-/- and MIP-1 alpha-/- mice, and this correlated with an enhanced control of parasite replication [21].
  • The disruption of the CCR2 and CCR5 signaling, alone or in combination, moderately prolong islet allograft survival [32].
  • Using antibodies specific for CCR5 and CCR8, the chemotactic response to MIP-1beta and TCA-3, respectively, was reduced significantly [33].

Analytical, diagnostic and therapeutic context of Ccr5


  1. Susceptibility of CCR5-Deficient Mice to Genital Herpes Simplex Virus Type 2 Is Linked to NK Cell Mobilization. Thapa, M., Kuziel, W.A., Carr, D.J. J. Virol. (2007) [Pubmed]
  2. CCR5 deficiency is not protective in the early stages of atherogenesis in apoE knockout mice. Kuziel, W.A., Dawson, T.C., Quinones, M., Garavito, E., Chenaux, G., Ahuja, S.S., Reddick, R.L., Maeda, N. Atherosclerosis (2003) [Pubmed]
  3. Chemokine receptor CCR5 deficiency exacerbates cerulein-induced acute pancreatitis in mice. Moreno, C., Nicaise, C., Gustot, T., Quertinmont, E., Nagy, N., Parmentier, M., Louis, H., Devi??re, J. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  4. Microglial activation varies in different models of Creutzfeldt-Jakob disease. Baker, C.A., Lu, Z.Y., Zaitsev, I., Manuelidis, L. J. Virol. (1999) [Pubmed]
  5. CCL5-CCR5 interaction provides antiapoptotic signals for macrophage survival during viral infection. Tyner, J.W., Uchida, O., Kajiwara, N., Kim, E.Y., Patel, A.C., O'Sullivan, M.P., Walter, M.J., Schwendener, R.A., Cook, D.N., Danoff, T.M., Holtzman, M.J. Nat. Med. (2005) [Pubmed]
  6. CCR5- and CXCR4-tropic HIV-1 are equally cytopathic for their T-cell targets in human lymphoid tissue. Grivel, J.C., Margolis, L.B. Nat. Med. (1999) [Pubmed]
  7. Apoptotic neutrophils and T cells sequester chemokines during immune response resolution through modulation of CCR5 expression. Ariel, A., Fredman, G., Sun, Y.P., Kantarci, A., Van Dyke, T.E., Luster, A.D., Serhan, C.N. Nat. Immunol. (2006) [Pubmed]
  8. HIV entry inhibitor TAK-779 attenuates atherogenesis in low-density lipoprotein receptor-deficient mice. van Wanrooij, E.J., Happé, H., Hauer, A.D., de Vos, P., Imanishi, T., Fujiwara, H., van Berkel, T.J., Kuiper, J. Arterioscler. Thromb. Vasc. Biol. (2005) [Pubmed]
  9. Characterization of antibody responses to purified HIV-1 gp120 glycoproteins fused with the molecular adjuvant C3d. Koch, M., Frazier, J., Sodroski, J., Wyatt, R. Virology (2005) [Pubmed]
  10. Periplocoside E inhibits experimental allergic encephalomyelitis by suppressing interleukin 12-dependent CCR5 expression and interferon-gamma-dependent CXCR3 expression in T lymphocytes. Zhu, Y.N., Zhong, X.G., Feng, J.Q., Yang, Y.F., Fu, Y.F., Ni, J., Liu, Q.F., Tang, W., Zhao, W.M., Zuo, J.P. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  11. SCH-C (SCH 351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of HIV-1 infection in vitro and in vivo. Strizki, J.M., Xu, S., Wagner, N.E., Wojcik, L., Liu, J., Hou, Y., Endres, M., Palani, A., Shapiro, S., Clader, J.W., Greenlee, W.J., Tagat, J.R., McCombie, S., Cox, K., Fawzi, A.B., Chou, C.C., Pugliese-Sivo, C., Davies, L., Moreno, M.E., Ho, D.D., Trkola, A., Stoddart, C.A., Moore, J.P., Reyes, G.R., Baroudy, B.M. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  12. Novel CCR5 monoclonal antibodies with potent and broad-spectrum anti-HIV activities. Ji, C., Brandt, M., Dioszegi, M., Jekle, A., Schwoerer, S., Challand, S., Zhang, J., Chen, Y., Zautke, L., Achhammer, G., Baehner, M., Kroetz, S., Heilek-Snyder, G., Schumacher, R., Cammack, N., Sankuratri, S. Antiviral Res. (2007) [Pubmed]
  13. Evolutionary genetics: Ambiguous role of CCR5 in Y. pestis infection. Elvin, S.J., Williamson, E.D., Scott, J.C., Smith, J.N., Pérez De Lema, G., Chilla, S., Clapham, P., Pfeffer, K., Schlöndorff, D., Luckow, B. Nature (2004) [Pubmed]
  14. Chemokine and chemokine receptor dynamics during genital chlamydial infection. Belay, T., Eko, F.O., Ananaba, G.A., Bowers, S., Moore, T., Lyn, D., Igietseme, J.U. Infect. Immun. (2002) [Pubmed]
  15. The contribution of chemokines and chemokine receptors to the rejection of fetal proislet allografts. Solomon, M.F., Kuziel, W.A., Simeonovic, C.J. Cell transplantation. (2004) [Pubmed]
  16. Abnormal immune response of CCR5-deficient mice to ocular infection with herpes simplex virus type 1. Carr, D.J., Ash, J., Lane, T.E., Kuziel, W.A. J. Gen. Virol. (2006) [Pubmed]
  17. Reduced intragraft mRNA expression of matrix metalloproteinases Mmp3, Mmp12, Mmp13 and Adam8, and diminished transplant arteriosclerosis in Ccr5-deficient mice. Luckow, B., Joergensen, J., Chilla, S., Li, J.P., Henger, A., Kiss, E., Wieczorek, G., Roth, L., Hartmann, N., Hoffmann, R., Kretzler, M., Nelson, P.J., Pérez de Lema, G., Maier, H., Wurst, W., Balling, R., Pfeffer, K., Gröne, H.J., Schlöndorff, D., Zerwes, H.G. Eur. J. Immunol. (2004) [Pubmed]
  18. Chemokine receptors Ccr1, Ccr2, and Ccr5 mediate neutrophil migration to postischemic tissue. Reichel, C.A., Khandoga, A., Anders, H.J., Schlöndorff, D., Luckow, B., Krombach, F. J. Leukoc. Biol. (2006) [Pubmed]
  19. Obstructive nephropathy in the mouse: progressive fibrosis correlates with tubulointerstitial chemokine expression and accumulation of CC chemokine receptor 2- and 5-positive leukocytes. Vielhauer, V., Anders, H.J., Mack, M., Cihak, J., Strutz, F., Stangassinger, M., Luckow, B., Gröne, H.J., Schlöndorff, D. J. Am. Soc. Nephrol. (2001) [Pubmed]
  20. FTY720-enhanced T cell homing is dependent on CCR2, CCR5, CCR7, and CXCR4: evidence for distinct chemokine compartments. Yopp, A.C., Fu, S., Honig, S.M., Randolph, G.J., Ding, Y., Krieger, N.R., Bromberg, J.S. J. Immunol. (2004) [Pubmed]
  21. Defects in the generation of IFN-gamma are overcome to control infection with Leishmania donovani in CC chemokine receptor (CCR) 5-, macrophage inflammatory protein-1 alpha-, or CCR2-deficient mice. Sato, N., Kuziel, W.A., Melby, P.C., Reddick, R.L., Kostecki, V., Zhao, W., Maeda, N., Ahuja, S.K., Ahuja, S.S. J. Immunol. (1999) [Pubmed]
  22. The chemokine receptor CCR5 is not a necessary inflammatory mediator in kainic acid-induced hippocampal injury: evidence for a compensatory effect by increased CCR2 and CCR3. Chen, Z., Yu, S., Bakhiet, M., Winblad, B., Zhu, J. J. Neurochem. (2003) [Pubmed]
  23. 17 beta-estradiol inhibits cytokine, chemokine, and chemokine receptor mRNA expression in the central nervous system of female mice with experimental autoimmune encephalomyelitis. Matejuk, A., Adlard, K., Zamora, A., Silverman, M., Vandenbark, A.A., Offner, H. J. Neurosci. Res. (2001) [Pubmed]
  24. Constitutive association of cell surface CCR5 and CXCR4 in the presence of CD4. Wang, J., Alvarez, R., Roderiquez, G., Guan, E., Norcross, M.A. J. Cell. Biochem. (2004) [Pubmed]
  25. CCR and CC chemokine expression in relation to Flt3 ligand-induced renal dendritic cell mobilization. Coates, P.T., Colvin, B.L., Ranganathan, A., Duncan, F.J., Lan, Y.Y., Shufesky, W.J., Zahorchak, A.F., Morelli, A.E., Thomson, A.W. Kidney Int. (2004) [Pubmed]
  26. The chemokine receptor CCR2 is involved in macrophage recruitment to the injured peripheral nervous system. Siebert, H., Sachse, A., Kuziel, W.A., Maeda, N., Brück, W. J. Neuroimmunol. (2000) [Pubmed]
  27. Active participation of CCR5(+)CD8(+) T lymphocytes in the pathogenesis of liver injury in graft-versus-host disease. Murai, M., Yoneyama, H., Harada, A., Yi, Z., Vestergaard, C., Guo, B., Suzuki, K., Asakura, H., Matsushima, K. J. Clin. Invest. (1999) [Pubmed]
  28. The role of CC chemokine receptor 5 (CCR5) in islet allograft rejection. Abdi, R., Smith, R.N., Makhlouf, L., Najafian, N., Luster, A.D., Auchincloss, H., Sayegh, M.H. Diabetes (2002) [Pubmed]
  29. Lack of chemokine receptor CCR5 promotes murine fulminant liver failure by preventing the apoptosis of activated CD1d-restricted NKT cells. Ajuebor, M.N., Aspinall, A.I., Zhou, F., Le, T., Yang, Y., Urbanski, S.J., Sidobre, S., Kronenberg, M., Hogaboam, C.M., Swain, M.G. J. Immunol. (2005) [Pubmed]
  30. Deficiency in CCR5 but not CCR1 protects against neointima formation in atherosclerosis-prone mice: involvement of IL-10. Zernecke, A., Liehn, E.A., Gao, J.L., Kuziel, W.A., Murphy, P.M., Weber, C. Blood (2006) [Pubmed]
  31. Experimental autoimmune encephalomyelitis on the SJL mouse: effect of gamma delta T cell depletion on chemokine and chemokine receptor expression in the central nervous system. Rajan, A.J., Asensio, V.C., Campbell, I.L., Brosnan, C.F. J. Immunol. (2000) [Pubmed]
  32. Differential expression of chemokines and chemokine receptors in murine islet allografts: the role of CCR2 and CCR5 signaling pathways. Schröppel, B., Zhang, N., Chen, P., Zang, W., Chen, D., Hudkins, K.L., Kuziel, W.A., Sung, R., Bromberg, J.S., Murphy, B. J. Am. Soc. Nephrol. (2004) [Pubmed]
  33. Increased responsiveness of murine eosinophils to MIP-1beta (CCL4) and TCA-3 (CCL1) is mediated by their specific receptors, CCR5 and CCR8. Oliveira, S.H., Lira, S., Martinez-A, C., Wiekowski, M., Sullivan, L., Lukacs, N.W. J. Leukoc. Biol. (2002) [Pubmed]
  34. Chemokine and chemokine receptor expression during initiation and resolution of immune complex glomerulonephritis. Anders, H.J., Vielhauer, V., Kretzler, M., Cohen, C.D., Segerer, S., Luckow, B., Weller, L., Gröne, H.J., Schlöndorff, D. J. Am. Soc. Nephrol. (2001) [Pubmed]
  35. CCR5 mediates specific migration of Toxoplasma gondii-primed CD8 lymphocytes to inflammatory intestinal epithelial cells. Luangsay, S., Kasper, L.H., Rachinel, N., Minns, L.A., Mennechet, F.J., Vandewalle, A., Buzoni-Gatel, D. Gastroenterology (2003) [Pubmed]
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