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Gene Review

Ccr7  -  chemokine (C-C motif) receptor 7

Mus musculus

Synonyms: C-C CKR-7, C-C chemokine receptor type 7, CC-CKR-7, CCR-7, CD197, ...
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Disease relevance of Ccr7

  • CONCLUSIONS: Induction of allergic asthma in mutant mice with impaired CCR7 responses results in characteristics that resemble severe asthma in human subjects, including severe bronchial lymphocytosis, eosinophilia, and neutrophilia, but not in enhancement in airway hyperreactivity [1].
  • Defective CCR7 expression on dendritic cells contributes to the development of visceral leishmaniasis [2].
  • Differential requirements for the chemokine receptor CCR7 in T cell activation during Listeria monocytogenes infection [3].
  • In the memory phase, CCR7-deficient mice maintained a stable LCMV-specific CTL population, predominantly in nonlymphoid organs, and rapidly mounted protective CTL responses against a challenge infection with a vaccinia virus recombinant for the gp33 epitope of LCMV [4].
  • In this study we investigated the impact of CCR7 on CD8(+) T cell responses by infecting CCR7(-/-) mice with lymphocytic choriomeningitis virus (LCMV) [4].

High impact information on Ccr7

  • Naïve and T helper 1 (TH1) cells, which express the chemokine receptor CCR7, are home to the periarteriolar lymphoid sheath, whereas activated TH2 cells, which lack CCR7, form rings at the periphery of the T cell zones near B cell follicles [5].
  • The inhibition of sphingosine-1-phosphate-mediated lymphocyte egress from the thymus led to the accumulation of mature thymocytes in the cortex of CCR7- or CCR7L-deficient mice, unlike the accumulation in the medulla of normal mice, thereby suggesting that mature thymocytes may be exported directly from the cortex in the absence of CCR7 signals [6].
  • It was recently shown that a chemokine signal via CCR7 is essential for the cortex-to-medulla migration of positively selected thymocytes in the thymus [6].
  • The present study shows that the developmental kinetics and the thymic export of mature thymocytes were undisturbed in adult mice lacking CCR7 or its ligands (CCR7L) [6].
  • However, the thymocytes that were generated in the absence of CCR7 or CCR7L were potent in causing autoimmune dacryoadenitis and sialadenitis in mice and were thus incapable of establishing central tolerance to organ-specific antigens [6].

Biological context of Ccr7


Anatomical context of Ccr7

  • Here we show in mice that natural killer (NK) cells, which are normally excluded from lymph nodes, are rapidly recruited in a CCR7-independent, CXCR3-dependent manner to lymph nodes on stimulation by the injection of mature DCs [11].
  • Here, we report that T(CM), unlike naive T cells, can home to PLNs in both a CCR7-dependent and -independent manner [12].
  • CXCL12 mediates CCR7-independent homing of central memory cells, but not naive T cells, in peripheral lymph nodes [12].
  • Using intravital microscopy, we find that B cell adhesion to high endothelial venules (HEVs) is disrupted when CCR7 and CXCR4 are predesensitized [13].
  • Thus, our study suggests a role for Jak tyrosine kinases during CCR7-mediated lymphocyte recirculation [14].

Associations of Ccr7 with chemical compounds

  • The CCR7 and CCR2 chemokine ligands are required for both T cell sequestration in LN and thymic T cell egress following FTY720 administration [15].
  • In isolated CD4+CD8+CCR7-thymocytes, a moderate 20-h pulse stimulation with a combination of the calcium ionophore ionomycin and the protein kinase C activator phorbol myristate acetate induced CCR7 expression and CD8 downregulation [16].
  • Induction of CCR7 expression in thymocytes requires both ERK signal and Ca(2+) signal [16].
  • Regulation of dendritic cell migration and adaptive immune response by leukotriene B4 receptors: a role for LTB4 in up-regulation of CCR7 expression and function [17].
  • However, our reverse transcription-polymerase chain reaction analysis revealed that Ad-infection resulted in the upregulation of the chemokine receptor CCR7 and downregulation of CCR6 in mBM-DCs and LPS-stimulated cells [18].

Regulatory relationships of Ccr7

  • Compared to naïve, type-1 and type-2 populations had reduced CCR7 and enhanced CXCR5 transcripts, consistent with a shift to memory cells [19].
  • It is suggested that CCR7 ligands activate Cdc42 and Rac, thereby inducing the endocytosis in mature DCs [10].

Other interactions of Ccr7


Analytical, diagnostic and therapeutic context of Ccr7

  • Effective immunotherapy was achieved with CCR7-expressing DCs, without the need to identify protective Leishmania antigens [2].
  • Coculture of DCs and apoptotic tumor cells resulted in decreased expression of CC chemokine receptor (CCR) 1 and increased CCR7 expression at mRNA level without alteration in other phenotypical markers on DCs [23].
  • Both mIL-10 and vIL-10 down-regulated the expression of CCR7 mRNA determined by RT-PCR, while mIL-10 up-regulated the expression of CCR5 transcripts [24].
  • CONCLUSIONS: These results suggest that CCR7-dependent processes support allograft rejection yet are dispensable for the rejection response [25].
  • In a heterotopic heart transplantation model CCR7 deficiency resulted in significantly prolonged but not indefinite allograft survival [26].


  1. Enhanced allergen-induced airway inflammation in paucity of lymph node T cell (plt) mutant mice. Grinnan, D., Sung, S.S., Dougherty, J.A., Knowles, A.R., Allen, M.B., Rose, C.E., Nakano, H., Gunn, M.D., Fu, S.M., Rose, C.E. J. Allergy Clin. Immunol. (2006) [Pubmed]
  2. Defective CCR7 expression on dendritic cells contributes to the development of visceral leishmaniasis. Ato, M., Stäger, S., Engwerda, C.R., Kaye, P.M. Nat. Immunol. (2002) [Pubmed]
  3. Differential requirements for the chemokine receptor CCR7 in T cell activation during Listeria monocytogenes infection. Kursar, M., Höpken, U.E., Koch, M., Köhler, A., Lipp, M., Kaufmann, S.H., Mittrücker, H.W. J. Exp. Med. (2005) [Pubmed]
  4. Impact of CCR7 on priming and distribution of antiviral effector and memory CTL. Junt, T., Scandella, E., Förster, R., Krebs, P., Krautwald, S., Lipp, M., Hengartner, H., Ludewig, B. J. Immunol. (2004) [Pubmed]
  5. The role of CCR7 in TH1 and TH2 cell localization and delivery of B cell help in vivo. Randolph, D.A., Huang, G., Carruthers, C.J., Bromley, L.E., Chaplin, D.D. Science (1999) [Pubmed]
  6. CCR7-dependent cortex-to-medulla migration of positively selected thymocytes is essential for establishing central tolerance. Kurobe, H., Liu, C., Ueno, T., Saito, F., Ohigashi, I., Seach, N., Arakaki, R., Hayashi, Y., Kitagawa, T., Lipp, M., Boyd, R.L., Takahama, Y. Immunity (2006) [Pubmed]
  7. Requirements for follicular exclusion and competitive elimination of autoantigen-binding B cells. Ekland, E.H., Forster, R., Lipp, M., Cyster, J.G. J. Immunol. (2004) [Pubmed]
  8. CC chemokine receptor 7-dependent and -independent pathways for lymphocyte homing: modulation by FTY720. Henning, G., Ohl, L., Junt, T., Reiterer, P., Brinkmann, V., Nakano, H., Hohenberger, W., Lipp, M., Förster, R. J. Exp. Med. (2001) [Pubmed]
  9. Cooperating mechanisms of CXCR5 and CCR7 in development and organization of secondary lymphoid organs. Ohl, L., Henning, G., Krautwald, S., Lipp, M., Hardtke, S., Bernhardt, G., Pabst, O., Förster, R. J. Exp. Med. (2003) [Pubmed]
  10. CCR7 ligands induce rapid endocytosis in mature dendritic cells with concomitant up-regulation of Cdc42 and Rac activities. Yanagawa, Y., Onoé, K. Blood (2003) [Pubmed]
  11. Induced recruitment of NK cells to lymph nodes provides IFN-gamma for T(H)1 priming. Martín-Fontecha, A., Thomsen, L.L., Brett, S., Gerard, C., Lipp, M., Lanzavecchia, A., Sallusto, F. Nat. Immunol. (2004) [Pubmed]
  12. CXCL12 mediates CCR7-independent homing of central memory cells, but not naive T cells, in peripheral lymph nodes. Scimone, M.L., Felbinger, T.W., Mazo, I.B., Stein, J.V., Von Andrian, U.H., Weninger, W. J. Exp. Med. (2004) [Pubmed]
  13. Chemokine requirements for B cell entry to lymph nodes and Peyer's patches. Okada, T., Ngo, V.N., Ekland, E.H., Förster, R., Lipp, M., Littman, D.R., Cyster, J.G. J. Exp. Med. (2002) [Pubmed]
  14. CCR7-mediated physiological lymphocyte homing involves activation of a tyrosine kinase pathway. Stein, J.V., Soriano, S.F., M'rini, C., Nombela-Arrieta, C., de Buitrago, G.G., Rodríguez-Frade, J.M., Mellado, M., Girard, J.P., Martínez-A, C. Blood (2003) [Pubmed]
  15. 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]
  16. Induction of CCR7 expression in thymocytes requires both ERK signal and Ca(2+) signal. Adachi, S., Kuwata, T., Miyaike, M., Iwata, M. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  17. Regulation of dendritic cell migration and adaptive immune response by leukotriene B4 receptors: a role for LTB4 in up-regulation of CCR7 expression and function. Del Prete, A., Shao, W.H., Mitola, S., Santoro, G., Sozzani, S., Haribabu, B. Blood (2007) [Pubmed]
  18. Gene transduction efficiency and maturation status in mouse bone marrow-derived dendritic cells infected with conventional or RGD fiber-mutant adenovirus vectors. Okada, N., Masunaga, Y., Okada, Y., Iiyama, S., Mori, N., Tsuda, T., Matsubara, A., Mizuguchi, H., Hayakawa, T., Fujita, T., Yamamoto, A. Cancer Gene Ther. (2003) [Pubmed]
  19. Population analysis of CD4+ T cell chemokine receptor transcript expression during in vivo type-1 (mycobacterial) and type-2 (schistosomal) immune responses. Chiu, B.C., Shang, X.Z., Stolberg, V.R., Komuniecki, E., Chensue, S.W. J. Leukoc. Biol. (2002) [Pubmed]
  20. The subpopulation of CD4+CD25+ splenocytes that delays adoptive transfer of diabetes expresses L-selectin and high levels of CCR7. Szanya, V., Ermann, J., Taylor, C., Holness, C., Fathman, C.G. J. Immunol. (2002) [Pubmed]
  21. Loss of Dendritic Cell Migration and Impaired Resistance to Leishmania donovani Infection in Mice Deficient in CCL19 and CCL21. Ato, M., Maroof, A., Zubairi, S., Nakano, H., Kakiuchi, T., Kaye, P.M. J. Immunol. (2006) [Pubmed]
  22. Regulation of T-lymphocyte trafficking by ICAM-1, MAdCAM-1, and CCR7 in microcirculation of appendicular and intestinal lymphoid tissues. Nagamatsu, H., Tsuzuki, Y., Matsuzaki, K., Miyazaki, J., Okada, Y., Hokari, R., Kawaguchi, A., Nagao, S., Itoh, K., Miura, S. Microcirculation (New York, N.Y. : 1994) (2004) [Pubmed]
  23. CC chemokine receptor-7 on dendritic cells is induced after interaction with apoptotic tumor cells: critical role in migration from the tumor site to draining lymph nodes. Hirao, M., Onai, N., Hiroishi, K., Watkins, S.C., Matsushima, K., Robbins, P.D., Lotze, M.T., Tahara, H. Cancer Res. (2000) [Pubmed]
  24. Mammalian and viral IL-10 enhance C-C chemokine receptor 5 but down-regulate C-C chemokine receptor 7 expression by myeloid dendritic cells: impact on chemotactic responses and in vivo homing ability. Takayama, T., Morelli, A.E., Onai, N., Hirao, M., Matsushima, K., Tahara, H., Thomson, A.W. J. Immunol. (2001) [Pubmed]
  25. Prolongation of allograft survival in ccr7-deficient mice. Beckmann, J.H., Yan, S., Lührs, H., Heid, B., Skubich, S., Förster, R., Hoffmann, M.W. Transplantation (2004) [Pubmed]
  26. The chemokine receptor CCR7 controls lymph node-dependent cytotoxic T cell priming in alloimmune responses. Höpken, U.E., Droese, J., Li, J.P., Joergensen, J., Breitfeld, D., Zerwes, H.G., Lipp, M. Eur. J. Immunol. (2004) [Pubmed]
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