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Gene Review

CCL19  -  chemokine (C-C motif) ligand 19

Homo sapiens

Synonyms: Beta-chemokine exodus-3, C-C motif chemokine 19, CK beta-11, CKb11, EBI1 ligand chemokine, ...
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Disease relevance of CCL19


High impact information on CCL19

  • Thus, MRP-1 regulates DC migration to lymph nodes, apparently by transporting LTC(4), which in turn promotes chemotaxis to CCL19 and mobilization of DCs from the epidermis [5].
  • We show that myosin containing the mutant ELC has abnormal function, map the mutant residues on the three-dimensional structure of myosin and suggest that the mutations disrupt the stretch activation response of the cardiac papillary muscles [6].
  • Instead activation of the AnTat 1.1C gene seems operated by reciprocal recombination between its own telomere and the telomere carrying the previous (AnTat 1.16) ELC [7].
  • 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 [8].
  • 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 [9].

Chemical compound and disease context of CCL19


Biological context of CCL19


Anatomical context of CCL19

  • The CCR7 ligand elc (CCL19) is transcytosed in high endothelial venules and mediates T cell recruitment [16].
  • In contrast, the majority of DC-Lamp(+) mature DCs in inflamed skin were totally negative for CCL19 and were surrounded by CCR7(-) memory-type T cells [17].
  • Differential expression of CCL19 by DC-Lamp+ mature dendritic cells in human lymph node versus chronically inflamed skin [17].
  • Moreover, proliferation of CD56(dim) CD16+ NK cells is costimulated by CCL19 and CCL21 [18].
  • We conclude that perivascular ELC is transcytosed to the luminal surfaces of HEVs and participates in CCR7-mediated triggering of lymphocyte arrest [16].

Associations of CCL19 with chemical compounds


Physical interactions of CCL19

  • CCR7 binds CCL19 and CCL21, causing the highly activated DCs to be trapped in the peripheral tissue site [21].
  • Transcription factor binding experiments demonstrated that Salmonella or Sendai virus infection increased the binding of classical p50+p65 and alternative p52+RelB NF-kappaB proteins to both of the CCL19 promoter NF-kappaB elements [20].

Regulatory relationships of CCL19

  • SLC and ELC were also shown to fully share receptors expressed on cultured normal T cells known to express CCR7 [22].
  • The expression of these chemokines and of CCL19 was dependent on bacteria-induced IFN-alpha/beta production [23].
  • However, CCL19 promotes 4-fold more ERK1/2 phosphorylation than does CCL21 [24].
  • MIP-3 beta protein concentrations were elevated in BALF from sarcoid patients compared with control subjects (p = 0.001) and in patients with chest X-ray stage II chemokine protein levels were increased compared with stage I (p = 0.003) [2].
  • Activation of DCs by CD40 ligand further up-regulated the expression of ELC (25-fold) [25].

Other interactions of CCL19

  • We termed this novel chemokine from EBI1-Ligand Chemokine as ELC (see below) [4].
  • However, MDC reactivity was consistently localized to the outer wall of Hassal's corpuscles, whereas ELC reactivity was often found in cells surrounding medullary vessels, but not in Hassal's corpuscles [26].
  • PARC mRNA was restricted to CD68+ macrophages (n = 14 of 18), whereas ELC mRNA was widely expressed by macrophages and intimal smooth muscle cells (SMC) in nearly all of the lesions examined (n = 12 of 14) [27].
  • By contrast, ELC production by CD30L-lacking medullary epithelial cells may induce the migration into periphery of mature thymocytes that have survived the process of negative selection [26].
  • CXCL10, CXCL12, and CCL19 were increased in the CSF of individuals with neuroinflammation [28].

Analytical, diagnostic and therapeutic context of CCL19


  1. 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]
  2. Expression of macrophage inflammatory protein-3 beta/CCL19 in pulmonary sarcoidosis. Gibejova, A., Mrazek, F., Subrtova, D., Sekerova, V., Szotkowska, J., Kolek, V., du Bois, R.M., Petrek, M. Am. J. Respir. Crit. Care Med. (2003) [Pubmed]
  3. Decreased serum level of macrophage inflammatory chemokine-3beta/CCL19 in preterm labor and delivery. Laudanski, P., Lemancewicz, A., Pierzynski, P., Akerlund, M., Laudanski, T. Eur. J. Obstet. Gynecol. Reprod. Biol. (2006) [Pubmed]
  4. 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]
  5. The leukotriene C(4) transporter MRP1 regulates CCL19 (MIP-3beta, ELC)-dependent mobilization of dendritic cells to lymph nodes. Robbiani, D.F., Finch, R.A., Jäger, D., Muller, W.A., Sartorelli, A.C., Randolph, G.J. Cell (2000) [Pubmed]
  6. Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle. Poetter, K., Jiang, H., Hassanzadeh, S., Master, S.R., Chang, A., Dalakas, M.C., Rayment, I., Sellers, J.R., Fananapazir, L., Epstein, N.D. Nat. Genet. (1996) [Pubmed]
  7. Modifications of a Trypanosoma b. brucei antigen gene repertoire by different DNA recombinational mechanisms. Pays, E., Delauw, M.F., Van Assel, S., Laurent, M., Vervoort, T., Van Meirvenne, N., Steinert, M. Cell (1983) [Pubmed]
  8. 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]
  9. 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]
  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. Epidermal Langerhans cell density in patients with pulmonary malignancies and chronic obstructive pulmonary disease. Shaieb, A.M., Berman, B., Smith, B., Krumpe, P. The Journal of dermatologic surgery and oncology. (1987) [Pubmed]
  12. 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]
  13. Secondary lymphoid organ chemokines are elevated in the cerebrospinal fluid during central nervous system inflammation. Pashenkov, M., Söderström, M., Link, H. J. Neuroimmunol. (2003) [Pubmed]
  14. Transgenic overexpression of the CC chemokine CCL21 disrupts T-cell migration. Christopherson, K.W., Campbell, J.J., Hromas, R.A. Blood (2001) [Pubmed]
  15. 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]
  16. 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]
  17. 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]
  18. Role of chemokines in the biology of natural killer cells. Robertson, M.J. J. Leukoc. Biol. (2002) [Pubmed]
  19. 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]
  20. Multiple NF-{kappa}B and IFN Regulatory Factor Family Transcription Factors Regulate CCL19 Gene Expression in Human Monocyte-Derived Dendritic Cells. Pietil??, T.E., Veckman, V., Lehtonen, A., Lin, R., Hiscott, J., Julkunen, I. J. Immunol. (2007) [Pubmed]
  21. Trapping of misdirected dendritic cells in the granulomatous lesions of giant cell arteritis. Krupa, W.M., Dewan, M., Jeon, M.S., Kurtin, P.J., Younge, B.R., Goronzy, J.J., Weyand, C.M. Am. J. Pathol. (2002) [Pubmed]
  22. 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]
  23. Lactobacilli and streptococci induce inflammatory chemokine production in human macrophages that stimulates Th1 cell chemotaxis. Veckman, V., Miettinen, M., Matikainen, S., Lande, R., Giacomini, E., Coccia, E.M., Julkunen, I. J. Leukoc. Biol. (2003) [Pubmed]
  24. 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]
  25. Quantitative analysis of chemokine expression by dendritic cell subsets in vitro and in vivo. Vissers, J.L., Hartgers, F.C., Lindhout, E., Teunissen, M.B., Figdor, C.G., Adema, G.J. J. Leukoc. Biol. (2001) [Pubmed]
  26. Macrophage-derived chemokine and EBI1-ligand chemokine attract human thymocytes in different stage of development and are produced by distinct subsets of medullary epithelial cells: possible implications for negative selection. Annunziato, F., Romagnani, P., Cosmi, L., Beltrame, C., Steiner, B.H., Lazzeri, E., Raport, C.J., Galli, G., Manetti, R., Mavilia, C., Vanini, V., Chantry, D., Maggi, E., Romagnani, S. J. Immunol. (2000) [Pubmed]
  27. Expression and cellular localization of the CC chemokines PARC and ELC in human atherosclerotic plaques. Reape, T.J., Rayner, K., Manning, C.D., Gee, A.N., Barnette, M.S., Burnand, K.G., Groot, P.H. Am. J. Pathol. (1999) [Pubmed]
  28. Phenotypic and functional analysis of T cells homing into the CSF of subjects with inflammatory diseases of the CNS. Giunti, D., Borsellino, G., Benelli, R., Marchese, M., Capello, E., Valle, M.T., Pedemonte, E., Noonan, D., Albini, A., Bernardi, G., Mancardi, G.L., Battistini, L., Uccelli, A. J. Leukoc. Biol. (2003) [Pubmed]
  29. Determinants of high-affinity binding and receptor activation in the N-terminus of CCL-19 (MIP-3 beta). Ott, T.R., Lio, F.M., Olshefski, D., Liu, X.J., Struthers, R.S., Ling, N. Biochemistry (2004) [Pubmed]
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