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Gene Review

CCL21  -  chemokine (C-C motif) ligand 21

Homo sapiens

Synonyms: 6Ckine, Beta-chemokine exodus-2, C-C motif chemokine 21, CKb9, ECL, ...
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Disease relevance of CCL21


Psychiatry related information on CCL21

  • Elimination of the diagnostic impact of 'co-occurrence of psychotic and affective symptoms' excluded FRS standalone individuals from the sample, increased overall homogeneity and resulted in a dichotomized sample according to SLC (46 positive vs. 47 negative) [5].

High impact information on CCL21

  • Here we show that antigen-engaged B cells have increased expression of CCR7, the receptor for the T-zone chemokines CCL19 and CCL21, and that they exhibit increased responsiveness to both chemoattractants [6].
  • 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].
  • 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 [7].
  • Here we demonstrate that T cell zone chemokines such as CCL21 are bound to the surface of lymph node dendritic cells [8].
  • Enhanced endothelial expression of ICAM-1 and CCL21 was linked to increased lymphocyte trafficking across HEVs [9].

Chemical compound and disease context of CCL21


Biological context of CCL21


Anatomical context of CCL21


Associations of CCL21 with chemical compounds


Physical interactions of CCL21

  • BACKGROUND AND AIMS: The chemokines CCL19 and CCL21 bind CCR7, which is involved in the organization of secondary lymphoid tissue and is expressed during chronic tissue inflammation [26].

Regulatory relationships of CCL21

  • SLC also induced a vigorous chemotactic response in CCR7-expressing L1.2 cells with a typical bell-shaped dose-response curve and a maximal migration at 10 nM [27].
  • Most blood vessels in tissue samples from patients with rheumatoid arthritis (85 +/- 10%) and ulcerative colitis (66 +/- 1%) expressed CCL21, and many perivascular CD45RA(+) naive T cells were found in these tissues, but not in psoriasis, where CCL21(+) vessels were rare (17 +/- 1%) [24].
  • Both CCL19 and CCL21 induce G protein activation and calcium mobilization with equal potency [28].
  • SLC and Epstein-Barr virus-induced molecule 1 ligand chemokine completely cross-desensitized the calcium response of each other, indicating that they share similar signaling pathways in DC [29].
  • This study demonstrated that CCL21 was an effective adjuvant to enhance TRP2-specific immunity induced by a plasmid DNA cancer vaccine [30].

Other interactions of CCL21


Analytical, diagnostic and therapeutic context of CCL21


  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. 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]
  3. 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]
  4. 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]
  5. Diagnostic Agreement of Schizophrenia Spectrum Disorders among Chronic Patients with Functional Psychoses. Jakobsen, K.D., Frederiksen, J.N., Parnas, J., Werge, T. Psychopathology. (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. 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]
  8. Surface-bound chemokines capture and prime T cells for synapse formation. Friedman, R.S., Jacobelli, J., Krummel, M.F. Nat. Immunol. (2006) [Pubmed]
  9. Fever-range thermal stress promotes lymphocyte trafficking across high endothelial venules via an interleukin 6 trans-signaling mechanism. Chen, Q., Fisher, D.T., Clancy, K.A., Gauguet, J.M., Wang, W.C., Unger, E., Rose-John, S., von Andrian, U.H., Baumann, H., Evans, S.S. Nat. Immunol. (2006) [Pubmed]
  10. HIV type 1 glycoprotein 120 inhibits human B cell chemotaxis to CXC chemokine ligand (CXCL) 12, CC chemokine ligand (CCL)20, and CCL21. Badr, G., Borhis, G., Treton, D., Moog, C., Garraud, O., Richard, Y. J. Immunol. (2005) [Pubmed]
  11. Effect of enprostil on serum gastrin and pepsinogen A and C levels in patients on long-term treatment with omeprazole. Meijer, J.L., Jansen, J.B., Biemond, I., Kuijpers, I.J., Lamers, C.B. Aliment. Pharmacol. Ther. (1994) [Pubmed]
  12. Octreotide induces apoptosis in the oxyntic mucosa. Erlandsen, S.E., Fykse, V., Waldum, H.L., Sandvik, A.K. Mol. Cell. Endocrinol. (2007) [Pubmed]
  13. The effect of vagotomy on enterochromaffin-like cells in Mastomys natalensis. Wängberg, B., Nilsson, O., Theodorsson, E., Modlin, I.M., Dahlström, A., Ahlman, H. J. Auton. Nerv. Syst. (1996) [Pubmed]
  14. Genistein, a tyrosine kinase inhibitor, reduces EGF-induced EGF receptor internalization and degradation in human hepatoma HepG2 cells. Yang, E.B., Wang, D.F., Mack, P., Cheng, L.Y. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  15. Transgenic overexpression of the CC chemokine CCL21 disrupts T-cell migration. Christopherson, K.W., Campbell, J.J., Hromas, R.A. Blood (2001) [Pubmed]
  16. Developmental stage-specific shift in responsiveness to chemokines during human B-cell development. Honczarenko, M., Glodek, A.M., Swierkowski, M., Na, I.K., Silberstein, L.E. Exp. Hematol. (2006) [Pubmed]
  17. Effects of chemokines on proliferation and apoptosis of human mesangial cells. Wörnle, M., Schmid, H., Merkle, M., Banas, B. BMC nephrology [electronic resource]. (2004) [Pubmed]
  18. Cathepsin D specifically cleaves the chemokines macrophage inflammatory protein-1 alpha, macrophage inflammatory protein-1 beta, and SLC that are expressed in human breast cancer. Wolf, M., Clark-Lewis, I., Buri, C., Langen, H., Lis, M., Mazzucchelli, L. Am. J. Pathol. (2003) [Pubmed]
  19. Cutting edge: activity of human adult microglia in response to CC chemokine ligand 21. Dijkstra, I.M., Hulshof, S., van der Valk, P., Boddeke, H.W., Biber, K. J. Immunol. (2004) [Pubmed]
  20. Differential expression of CCL19 by DC-Lamp+ mature dendritic cells in human lymph node versus chronically inflamed skin. Katou, F., Ohtani, H., Nakayama, T., Nagura, H., Yoshie, O., Motegi, K. J. Pathol. (2003) [Pubmed]
  21. Role of chemokines in the biology of natural killer cells. Robertson, M.J. J. Leukoc. Biol. (2002) [Pubmed]
  22. Rho kinase is required for CCR7-mediated polarization and chemotaxis of T lymphocytes. Bardi, G., Niggli, V., Loetscher, P. FEBS Lett. (2003) [Pubmed]
  23. CCL19/CCL21-triggered signal transduction and migration of dendritic cells requires prostaglandin E2. Scandella, E., Men, Y., Legler, D.F., Gillessen, S., Prikler, L., Ludewig, B., Groettrup, M. Blood (2004) [Pubmed]
  24. Naive T cell recruitment to nonlymphoid tissues: a role for endothelium-expressed CC chemokine ligand 21 in autoimmune disease and lymphoid neogenesis. Weninger, W., Carlsen, H.S., Goodarzi, M., Moazed, F., Crowley, M.A., Baekkevold, E.S., Cavanagh, L.L., von Andrian, U.H. J. Immunol. (2003) [Pubmed]
  25. Long-lived immature dendritic cells mediated by TRANCE-RANK interaction. Cremer, I., Dieu-Nosjean, M.C., Maréchal, S., Dezutter-Dambuyant, C., Goddard, S., Adams, D., Winter, N., Menetrier-Caux, C., Sautès-Fridman, C., Fridman, W.H., Mueller, C.G. Blood (2002) [Pubmed]
  26. 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]
  27. 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]
  28. Differential desensitization, receptor phosphorylation, beta-arrestin recruitment, and ERK1/2 activation by the two endogenous ligands for the CC chemokine receptor 7. Kohout, T.A., Nicholas, S.L., Perry, S.J., Reinhart, G., Junger, S., Struthers, R.S. J. Biol. Chem. (2004) [Pubmed]
  29. Secondary lymphoid-tissue chemokine (SLC) is chemotactic for mature dendritic cells. Chan, V.W., Kothakota, S., Rohan, M.C., Panganiban-Lustan, L., Gardner, J.P., Wachowicz, M.S., Winter, J.A., Williams, L.T. Blood (1999) [Pubmed]
  30. Enhancement of Immunity by a DNA Melanoma Vaccine against TRP2 with CCL21 as an Adjuvant. Yamano, T., Kaneda, Y., Huang, S., Hiramatsu, S.H., Hoon, D.S. Mol. Ther. (2006) [Pubmed]
  31. Cutting edge: species specificity of the CC chemokine 6Ckine signaling through the CXC chemokine receptor CXCR3: human 6Ckine is not a ligand for the human or mouse CXCR3 receptors. Jenh, C.H., Cox, M.A., Kaminski, H., Zhang, M., Byrnes, H., Fine, J., Lundell, D., Chou, C.C., Narula, S.K., Zavodny, P.J. J. Immunol. (1999) [Pubmed]
  32. Involvement of Chemokine Receptor CCR6 in Colorectal Cancer Metastasis. Rubie, C., Oliveira, V., Kempf, K., Wagner, M., Tilton, B., Rau, B., Kruse, B., Konig, J., Schilling, M. Tumour Biol. (2006) [Pubmed]
  33. Chemokine receptor expressions and responsiveness of cord blood T cells. Sato, K., Kawasaki, H., Nagayama, H., Enomoto, M., Morimoto, C., Tadokoro, K., Juji, T., Takahashi, T. J. Immunol. (2001) [Pubmed]
  34. Molecular cloning of a novel human CC chemokine secondary lymphoid-tissue chemokine that is a potent chemoattractant for lymphocytes and mapped to chromosome 9p13. Nagira, M., Imai, T., Hieshima, K., Kusuda, J., Ridanpää, M., Takagi, S., Nishimura, M., Kakizaki, M., Nomiyama, H., Yoshie, O. J. Biol. Chem. (1997) [Pubmed]
  35. The chemokine SLC is expressed in T cell areas of lymph nodes and mucosal lymphoid tissues and attracts activated T cells via CCR7. Willimann, K., Legler, D.F., Loetscher, M., Roos, R.S., Delgado, M.B., Clark-Lewis, I., Baggiolini, M., Moser, B. Eur. J. Immunol. (1998) [Pubmed]
  36. Soluble expression of recombinant human secondary lymphoid chemokine (SLC) in E. coli and research on its in vitro and in vivo bioactivity. Chun, L., Yin, C.C., Song, J.Z., Liu, M.X., Piao, J.H., Lin, Q., Wang, X.B., Huang, H.L. J. Biochem. (2004) [Pubmed]
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