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Gene Review

CCR7  -  chemokine (C-C motif) receptor 7

Homo sapiens

Synonyms: BLR2, C-C CKR-7, C-C chemokine receptor type 7, CC-CKR-7, CCR-7, ...
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Disease relevance of CCR7


Psychiatry related information on CCR7


High impact information on CCR7

  • In mice lacking lymphoid CCL19 and CCL21 chemokines, or with B cells that lack CCR7, antigen engagement fails to cause movement to the T zone [6].
  • We investigated this issue by analysing the expression of the chemokine receptor CCR7, which defines distinct subsets of naive and memory T lymphocytes with different homing and effector capacities and antiviral immune responses to HIV and cytomegalovirus [7].
  • Another CC chemokine CCL21, which shares CCR7 with CCL19 but has a unique C-terminal extension containing positively charged amino acids, failed to show involvement in thymic emigration [8].
  • Neonatal appearance of circulating T cells was defective in CCL19-neutralized mice as well as in CCR7-deficient mice but not in CCL21-neutralized mice [8].
  • Role for CCR7 ligands in the emigration of newly generated T lymphocytes from the neonatal thymus [8].

Chemical compound and disease context of CCR7


Biological context of CCR7

  • Despite increased efficiency of uptake, interaction between iC3b-opsonized apoptotic cells and iDCs down-regulated the expression of major histocompatibility complex class II, CD86, CC chemokine receptor (CCR)2, CCR5, and beta2-integrins (P < 0.001), and up-regulated expression of CCR7 (P < 0.001) [14].
  • Cultured HSCs expressed functional CCR7, the activation of which stimulated cell migration and accelerated wound healing in an in vitro model [2].
  • The receptor for CCL21, CCR7, was also found to be highly expressed on the infiltrating T cells, most of which expressed the memory CD45Ro phenotype [15].
  • Finally, CCR7 up-regulation in DCs exposed to LPS as well as migration toward CCL19/MIP-3beta were strongly impaired [16].
  • Concomitantly, the expression of CCR7 and the migration to its ligand EBI1 ligand chemokine (ELC)/macrophage inflammatory protein (MIP)-3beta, a chemokine expressed in lymphoid organs, were strongly up-regulated, though with slower kinetics (24-48 h) [17].

Anatomical context of CCR7


Associations of CCR7 with chemical compounds


Physical interactions of CCR7


Regulatory relationships of CCR7

  • CONCLUSIONS: Expression of CCL21 during chronic hepatitis C is implicated in the recruitment of T lymphocytes and the organization of inflammatory lymphoid tissue and may promote fibrogenesis in the inflamed areas via activation of CCR7 on HSCs [2].
  • SLC and ELC were also shown to fully share receptors expressed on cultured normal T cells known to express CCR7 [28].
  • The strong allergen dinitrochlorobenzene slightly increased CCR7 expression on DCs but down-regulated CCR1 surface expression [29].
  • CCR7 transcripts were minimally expressed in ex vivo and proliferating WC1(+)gammadelta T cells and CXCR5 expression was negligible [30].
  • IL-4 promotes expression of CCR7, a marker linked to existing models of CD8(+) T cell differentiation [31].
  • EP2 and EP4 agonists stimulated CCR7 in MCF-7 cells, whereas antagonists or small hairpin RNA of EP2 and EP4 attenuated CCR7 in MDA-MB-231 cells [32].

Other interactions of CCR7

  • CD45RA(+)FOXP3(+) T cells mainly express lymphoid tissue homing receptors (CD62L, CCR7, and CXCR4), while CD45RO(+)FOXP3(+) T cells highly express both Th1 and Th2-associated trafficking receptors along with the lymphoid tissue homing receptors at reduced frequencies [33].
  • By stably expressing five CC chemokine receptors (CCR1 to 5) and five orphan receptors, ELC-SEAP was found to bind specifically to an orphan receptor EBI1 [34].
  • Within these samples, tumor mycosis fungoides cells exhibited high levels of CCR7, a chemokine receptor central for the entry of T cells to lymphatic tissue [35].
  • CXCR4 expression on lymphocytes from septic patients was increased whereas CCR5 was decreased and CCR7 was unchanged [24].
  • The mean fluorescent intensity (MFI) of the chemokine receptor expression on B-CLL cells was compared with normal controls and was not significantly different, except for an increase in the median expression of CXCR3 (P = .003) and CCR7 (P = .001) on B-CLL cells [36].

Analytical, diagnostic and therapeutic context of CCR7


  1. Involvement of chemokine receptors in breast cancer metastasis. Müller, A., Homey, B., Soto, H., Ge, N., Catron, D., Buchanan, M.E., McClanahan, T., Murphy, E., Yuan, W., Wagner, S.N., Barrera, J.L., Mohar, A., Verástegui, E., Zlotnik, A. Nature (2001) [Pubmed]
  2. The chemokine CCL21 modulates lymphocyte recruitment and fibrosis in chronic hepatitis C. Bonacchi, A., Petrai, I., Defranco, R.M., Lazzeri, E., Annunziato, F., Efsen, E., Cosmi, L., Romagnani, P., Milani, S., Failli, P., Batignani, G., Liotta, F., Laffi, G., Pinzani, M., Gentilini, P., Marra, F. Gastroenterology (2003) [Pubmed]
  3. Secondary lymphoid tissue chemokine (SLC/CCL21)/CCR7 signaling regulates fibrocytes in renal fibrosis. Sakai, N., Wada, T., Yokoyama, H., Lipp, M., Ueha, S., Matsushima, K., Kaneko, S. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  4. CD30 triggering by agonistic antibodies regulates CXCR4 expression and CXCL12 chemotactic activity in the cell line L540. Vinante, F., Rigo, A., Scupoli, M.T., Pizzolo, G. Blood (2002) [Pubmed]
  5. The Multiple Personalities of the Chemokine Receptor CCR7 in Dendritic Cells. Sánchez-Sánchez, N., Riol-Blanco, L., Rodríguez-Fernández, J.L. J. Immunol. (2006) [Pubmed]
  6. Balanced responsiveness to chemoattractants from adjacent zones determines B-cell position. Reif, K., Ekland, E.H., Ohl, L., Nakano, H., Lipp, M., Förster, R., Cyster, J.G. Nature (2002) [Pubmed]
  7. Skewed maturation of memory HIV-specific CD8 T lymphocytes. Champagne, P., Ogg, G.S., King, A.S., Knabenhans, C., Ellefsen, K., Nobile, M., Appay, V., Rizzardi, G.P., Fleury, S., Lipp, M., Förster, R., Rowland-Jones, S., Sékaly, R.P., McMichael, A.J., Pantaleo, G. Nature (2001) [Pubmed]
  8. Role for CCR7 ligands in the emigration of newly generated T lymphocytes from the neonatal thymus. Ueno, T., Hara, K., Willis, M.S., Malin, M.A., Höpken, U.E., Gray, D.H., Matsushima, K., Lipp, M., Springer, T.A., Boyd, R.L., Yoshie, O., Takahama, Y. Immunity (2002) [Pubmed]
  9. The chemokine receptor CCR7 and alpha4 integrin are important for migration of chronic lymphocytic leukemia cells into lymph nodes. Till, K.J., Lin, K., Zuzel, M., Cawley, J.C. Blood (2002) [Pubmed]
  10. Chemokine receptor CCR7 induces intracellular signaling that inhibits apoptosis of mature dendritic cells. Sánchez-Sánchez, N., Riol-Blanco, L., de la Rosa, G., Puig-Kröger, A., García-Bordas, J., Martín, D., Longo, N., Cuadrado, A., Cabañas, C., Corbí, A.L., Sánchez-Mateos, P., Rodríguez-Fernández, J.L. Blood (2004) [Pubmed]
  11. Epigenetic up-regulation of C-C chemokine receptor 7 and C-X-C chemokine receptor 4 expression in melanoma cells. Mori, T., Kim, J., Yamano, T., Takeuchi, H., Huang, S., Umetani, N., Koyanagi, K., Hoon, D.S. Cancer Res. (2005) [Pubmed]
  12. Role of homeostatic chemokine and sphingosine-1-phosphate receptors in the organization of lymphoid tissue. Müller, G., Reiterer, P., Höpken, U.E., Golfier, S., Lipp, M. Ann. N. Y. Acad. Sci. (2003) [Pubmed]
  13. Expression of the chemokine receptor BLR2/EBI1 is specifically transactivated by Epstein-Barr virus nuclear antigen 2. Burgstahler, R., Kempkes, B., Steube, K., Lipp, M. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  14. Opsonization of apoptotic cells by autologous iC3b facilitates clearance by immature dendritic cells, down-regulates DR and CD86, and up-regulates CC chemokine receptor 7. Verbovetski, I., Bychkov, H., Trahtemberg, U., Shapira, I., Hareuveni, M., Ben-Tal, O., Kutikov, I., Gill, O., Mevorach, D. J. Exp. Med. (2002) [Pubmed]
  15. Endothelial induction of the T-cell chemokine CCL21 in T-cell autoimmune diseases. Christopherson, K.W., Hood, A.F., Travers, J.B., Ramsey, H., Hromas, R.A. Blood (2003) [Pubmed]
  16. Proteasome inhibitor bortezomib modulates TLR4-induced dendritic cell activation. Nencioni, A., Schwarzenberg, K., Brauer, K.M., Schmidt, S.M., Ballestrero, A., Grünebach, F., Brossart, P. Blood (2006) [Pubmed]
  17. Differential regulation of chemokine receptors during dendritic cell maturation: a model for their trafficking properties. Sozzani, S., Allavena, P., D'Amico, G., Luini, W., Bianchi, G., Kataura, M., Imai, T., Yoshie, O., Bonecchi, R., Mantovani, A. J. Immunol. (1998) [Pubmed]
  18. 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]
  19. The CCR7 ligand elc (CCL19) is transcytosed in high endothelial venules and mediates T cell recruitment. Baekkevold, E.S., Yamanaka, T., Palframan, R.T., Carlsen, H.S., Reinholt, F.P., von Andrian, U.H., Brandtzaeg, P., Haraldsen, G. J. Exp. Med. (2001) [Pubmed]
  20. 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]
  21. Prostaglandin E2 is a key factor for CCR7 surface expression and migration of monocyte-derived dendritic cells. Scandella, E., Men, Y., Gillessen, S., Förster, R., Groettrup, M. Blood (2002) [Pubmed]
  22. 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. Kim, C.H., Johnston, B., Butcher, E.C. Blood (2002) [Pubmed]
  23. The impact of CCR7 and CXCR5 on lymphoid organ development and systemic immunity. Müller, G., Höpken, U.E., Lipp, M. Immunol. Rev. (2003) [Pubmed]
  24. Up-regulation of functional CXCR4 expression on human lymphocytes in sepsis. Ding, Z., Jia, S.H., Marshall, J.C., Downey, G.P., Waddell, T.K. Crit. Care Med. (2006) [Pubmed]
  25. Characterization of the molecular pharmacology of AMD3100: a specific antagonist of the G-protein coupled chemokine receptor, CXCR4. Fricker, S.P., Anastassov, V., Cox, J., Darkes, M.C., Grujic, O., Idzan, S.R., Labrecque, J., Lau, G., Mosi, R.M., Nelson, K.L., Qin, L., Santucci, Z., Wong, R.S. Biochem. Pharmacol. (2006) [Pubmed]
  26. BLR-1 and BLR-2, key regulatory elements of photoconidiation and mycelial growth in Trichoderma atroviride. Casas-Flores, S., Rios-Momberg, M., Bibbins, M., Ponce-Noyola, P., Herrera-Estrella, A. Microbiology (Reading, Engl.) (2004) [Pubmed]
  27. Induction of G protein-coupled peptide receptor EBI 1 by human herpesvirus 6 and 7 infection in CD4+ T cells. Hasegawa, H., Utsunomiya, Y., Yasukawa, M., Yanagisawa, K., Fujita, S. J. Virol. (1994) [Pubmed]
  28. Secondary lymphoid-tissue chemokine is a functional ligand for the CC chemokine receptor CCR7. Yoshida, R., Nagira, M., Kitaura, M., Imagawa, N., Imai, T., Yoshie, O. J. Biol. Chem. (1998) [Pubmed]
  29. Regulation by allergens of chemokine receptor expression on in vitro-generated dendritic cells. Jugdé, F., Boissier, C., Rougier-Larzat, N., Corlu, A., Chesné, C., Semana, G., Heresbach, D. Toxicology (2005) [Pubmed]
  30. Molecular cloning of bovine chemokine receptors and expression by WC1+ gammadelta T cells. Blumerman, S.L., Wang, F., Herzig, C.T., Baldwin, C.L. Dev. Comp. Immunol. (2007) [Pubmed]
  31. Interleukin-4 promotes human CD8 T cell expression of CCR7. Seneviratne, S.L., Black, A.P., Jones, L., di Gleria, K., Bailey, A.S., Ogg, G.S. Immunology (2007) [Pubmed]
  32. Cyclooxygenase-2 up-regulates CCR7 via EP2/EP4 receptor signaling pathways to enhance lymphatic invasion of breast cancer cells. Pan, M.R., Hou, M.F., Chang, H.C., Hung, W.C. J. Biol. Chem. (2008) [Pubmed]
  33. Regulation of trafficking receptor expression in human forkhead box P3+ regulatory T cells. Lim, H.W., Broxmeyer, H.E., Kim, C.H. J. Immunol. (2006) [Pubmed]
  34. Molecular cloning of a novel human CC chemokine EBI1-ligand chemokine that is a specific functional ligand for EBI1, CCR7. Yoshida, R., Imai, T., Hieshima, K., Kusuda, J., Baba, M., Kitaura, M., Nishimura, M., Kakizaki, M., Nomiyama, H., Yoshie, O. J. Biol. Chem. (1997) [Pubmed]
  35. Chemokine receptor expression on neoplastic and reactive T cells in the skin at different stages of mycosis fungoides. Kallinich, T., Muche, J.M., Qin, S., Sterry, W., Audring, H., Kroczek, R.A. J. Invest. Dermatol. (2003) [Pubmed]
  36. Expression of the chemokine receptors CXCR4 and CCR7 and disease progression in B-cell chronic lymphocytic leukemia/ small lymphocytic lymphoma. Ghobrial, I.M., Bone, N.D., Stenson, M.J., Novak, A., Hedin, K.E., Kay, N.E., Ansell, S.M. Mayo Clin. Proc. (2004) [Pubmed]
  37. Increased chemokine receptor CCR7/EBI1 expression enhances the infiltration of lymphoid organs by adult T-cell leukemia cells. Hasegawa, H., Nomura, T., Kohno, M., Tateishi, N., Suzuki, Y., Maeda, N., Fujisawa, R., Yoshie, O., Fujita, S. Blood (2000) [Pubmed]
  38. CCL21 chemokine regulates chemokine receptor CCR7 bearing malignant melanoma cells. Takeuchi, H., Fujimoto, A., Tanaka, M., Yamano, T., Hsueh, E., Hoon, D.S. Clin. Cancer Res. (2004) [Pubmed]
  39. EBI1-ligand chemokine (ELC) attracts a broad spectrum of lymphocytes: activated T cells strongly up-regulate CCR7 and efficiently migrate toward ELC. Yoshida, R., Nagira, M., Imai, T., Baba, M., Takagi, S., Tabira, Y., Akagi, J., Nomiyama, H., Yoshie, O. Int. Immunol. (1998) [Pubmed]
  40. Differential migration behavior and chemokine production by myeloid and plasmacytoid dendritic cells. Penna, G., Vulcano, M., Sozzani, S., Adorini, L. Hum. Immunol. (2002) [Pubmed]
  41. Association of CXCR4 and CCR7 chemokine receptor expression and lymph node metastasis in human cervical cancer. Kodama, J., Hasengaowa, n.u.l.l., Kusumoto, T., Seki, N., Matsuo, T., Ojima, Y., Nakamura, K., Hongo, A., Hiramatsu, Y. Ann. Oncol. (2007) [Pubmed]
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