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Gene Review

Ccl21b  -  chemokine (C-C motif) ligand 21B

Mus musculus

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Disease relevance of Ccl21a


High impact information on Ccl21a

  • CCL19 and CCL21 induce a potent proinflammatory differentiation program in licensed dendritic cells [6].
  • The residual stromal cells and endothelium produced sufficient CCL21 to direct the migration of DCs transferred from naïve mice [7].
  • Macrophage inflammatory protein 1alpha attracted blood DC precursors to the sinusoidal granuloma, whereas secondary lymphoid organ chemokine (SLC) attracted mature DCs to the newly identified PALT [8].
  • Desensitization of the TCA-4 receptor, CC chemokine receptor 7 (CCR7), blocked T(GFP) cell adherence in wild-type HEVs, whereas desensitization to stromal cell-derived factor (SDF)-1alpha (the ligand for CXC chemokine receptor 4 [CXCR4]) did not affect T(GFP) cell behavior [2].
  • We conclude that TCA-4 is both required and sufficient for LFA-1 activation on rolling T cells in PLN HEVs [2].

Biological context of Ccl21a


Anatomical context of Ccl21a


Associations of Ccl21a with chemical compounds

  • TCA-4 was constitutively presented on the luminal surface of HEVs, where it was required for LFA-1 activation on rolling T(GFP) cells [2].
  • RESULTS: It was found that pretreatment with small doses of CCL21 prevented the death of normal murine marrow progenitors from the toxic effects of Ara-C [14].
  • The increasing blood glucose values appeared to be consistent with an increasing CCL21 expression by the endothelial lining, especially on the surface of LECs adjacent to the infiltrated islets and tissues [15].
  • FTY720-mediated LN homing events further downstream are dependent on CCL19, CCL21, VLA-4alpha, and CD44 [16].
  • Finally, preincubation of BMDC with LPS in presence of the specific beta2-AR agonist salbutamol impaired their chemotactic response to CCL19 and CCL21 and this effect was neutralized by anti-IL-10 mAb [17].

Regulatory relationships of Ccl21a


Other interactions of Ccl21a

  • In this study, we report that following Leishmania donovani infection of mice, the migration of splenic DC is regulated by the CCR7 ligands CCL19/CCL21 [12].
  • Here, we used intravital microscopy of murine PLNs to study the role of thymus-derived chemotactic agent (TCA)-4 (secondary lymphoid tissue chemokine, 6Ckine, Exodus-2) in homing of adoptively transferred T cells from T-GFP mice, a transgenic strain that expresses green fluorescent protein (GFP) selectively in naive T lymphocytes (T(GFP) cells) [2].
  • When expressed in transgenic pancreas, both forms of CCL21 were capable of inducing the formation of lymph node-like structures composed primarily of T and B cells and a few dendritic cells [11].
  • However, fetal thymus colonization was markedly diminished by neutralizing antibodies specific for CCL21 and CCL25, but not affected by anti-CXCL12 antibody [20].
  • Among the chemokines produced by the fetal thymus, CCL21, CCL25, and CXCL12 could attract CD4(-)CD8(-)CD25(-)CD44+ fetal thymocytes [20].

Analytical, diagnostic and therapeutic context of Ccl21a


  1. The role of chemokines in the microenvironmental control of T versus B cell arrest in Peyer's patch high endothelial venules. Warnock, R.A., Campbell, J.J., Dorf, M.E., Matsuzawa, A., McEvoy, L.M., Butcher, E.C. J. Exp. Med. (2000) [Pubmed]
  2. The CC chemokine thymus-derived chemotactic agent 4 (TCA-4, secondary lymphoid tissue chemokine, 6Ckine, exodus-2) triggers lymphocyte function-associated antigen 1-mediated arrest of rolling T lymphocytes in peripheral lymph node high endothelial venules. Stein, J.V., Rot, A., Luo, Y., Narasimhaswamy, M., Nakano, H., Gunn, M.D., Matsuzawa, A., Quackenbush, E.J., Dorf, M.E., von Andrian, U.H. J. Exp. Med. (2000) [Pubmed]
  3. A ligand for the chemokine receptor CCR7 can influence the homeostatic proliferation of CD4 T cells and progression of autoimmunity. Ploix, C., Lo, D., Carson, M.J. J. Immunol. (2001) [Pubmed]
  4. Blocking programmed death-1 ligand-PD-1 interactions by local gene therapy results in enhancement of antitumor effect of secondary lymphoid tissue chemokine. He, Y.F., Zhang, G.M., Wang, X.H., Zhang, H., Yuan, Y., Li, D., Feng, Z.H. J. Immunol. (2004) [Pubmed]
  5. Blockade of secondary lymphoid tissue chemokine exacerbates Propionibacterium acnes-induced acute lung inflammation. Itakura, M., Tokuda, A., Kimura, H., Nagai, S., Yoneyama, H., Onai, N., Ishikawa, S., Kuriyama, T., Matsushima, K. J. Immunol. (2001) [Pubmed]
  6. CCL19 and CCL21 induce a potent proinflammatory differentiation program in licensed dendritic cells. Marsland, B.J., Bättig, P., Bauer, M., Ruedl, C., Lässing, U., Beerli, R.R., Dietmeier, K., Ivanova, L., Pfister, T., Vogt, L., Nakano, H., Nembrini, C., Saudan, P., Kopf, M., Bachmann, M.F. Immunity (2005) [Pubmed]
  7. 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]
  8. Regulation by chemokines of circulating dendritic cell precursors, and the formation of portal tract-associated lymphoid tissue, in a granulomatous liver disease. Yoneyama, H., Matsuno, K., Zhang, Y., Murai, M., Itakura, M., Ishikawa, S., Hasegawa, G., Naito, M., Asakura, H., Matsushima, K. J. Exp. Med. (2001) [Pubmed]
  9. Gene duplications at the chemokine locus on mouse chromosome 4: multiple strain-specific haplotypes and the deletion of secondary lymphoid-organ chemokine and EBI-1 ligand chemokine genes in the plt mutation. Nakano, H., Gunn, M.D. J. Immunol. (2001) [Pubmed]
  10. Identification of a new mouse beta-chemokine, thymus-derived chemotactic agent 4, with activity on T lymphocytes and mesangial cells. Tanabe, S., Lu, Z., Luo, Y., Quackenbush, E.J., Berman, M.A., Collins-Racie, L.A., Mi, S., Reilly, C., Lo, D., Jacobs, K.A., Dorf, M.E. J. Immunol. (1997) [Pubmed]
  11. Ectopic expression of the murine chemokines CCL21a and CCL21b induces the formation of lymph node-like structures in pancreas, but not skin, of transgenic mice. Chen, S.C., Vassileva, G., Kinsley, D., Holzmann, S., Manfra, D., Wiekowski, M.T., Romani, N., Lira, S.A. J. Immunol. (2002) [Pubmed]
  12. 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]
  13. The reduced expression of 6Ckine in the plt mouse results from the deletion of one of two 6Ckine genes. Vassileva, G., Soto, H., Zlotnik, A., Nakano, H., Kakiuchi, T., Hedrick, J.A., Lira, S.A. J. Exp. Med. (1999) [Pubmed]
  14. The chemokine CCL21 protects normal marrow progenitors from Ara-C cytotoxicity. Hromas, R., Cooper, S., Broxmeyer, H.E. Cancer Chemother. Pharmacol. (2002) [Pubmed]
  15. Histochemical analysis of lymphatic endothelial cells in the pancreas of non-obese diabetic mice. Qu, P., Ji, R.C., Kato, S. J. Anat. (2003) [Pubmed]
  16. FTY720 stimulates multidrug transporter- and cysteinyl leukotriene-dependent T cell chemotaxis to lymph nodes. Honig, S.M., Fu, S., Mao, X., Yopp, A., Gunn, M.D., Randolph, G.J., Bromberg, J.S. J. Clin. Invest. (2003) [Pubmed]
  17. Langerhans cells beta 2-adrenoceptors: role in migration, cytokine production, Th priming and contact hypersensitivity. Maestroni, G.J., Mazzola, P. J. Neuroimmunol. (2003) [Pubmed]
  18. Coexpression of the chemokines ELC and SLC by T zone stromal cells and deletion of the ELC gene in the plt/plt mouse. Luther, S.A., Tang, H.L., Hyman, P.L., Farr, A.G., Cyster, J.G. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  19. Secondary lymphoid tissue chemokine (CCL21) activates CXCR3 to trigger a Cl- current and chemotaxis in murine microglia. Rappert, A., Biber, K., Nolte, C., Lipp, M., Schubel, A., Lu, B., Gerard, N.P., Gerard, C., Boddeke, H.W., Kettenmann, H. J. Immunol. (2002) [Pubmed]
  20. The role of CCL21 in recruitment of T-precursor cells to fetal thymi. Liu, C., Ueno, T., Kuse, S., Saito, F., Nitta, T., Piali, L., Nakano, H., Kakiuchi, T., Lipp, M., Hollander, G.A., Takahama, Y. Blood (2005) [Pubmed]
  21. CXCL9 antagonism further extends prolonged cardiac allograft survival in CCL19/CCL21-deficient mice. Colvin, B.L., Wang, Z., Nakano, H., Wu, W., Kakiuchi, T., Fairchild, R.L., Thomson, A.W. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. (2005) [Pubmed]
  22. Functional expression of the lymphoid chemokines CCL19 (ELC) and CCL 21 (SLC) at the blood-brain barrier suggests their involvement in G-protein-dependent lymphocyte recruitment into the central nervous system during experimental autoimmune encephalomyelitis. Alt, C., Laschinger, M., Engelhardt, B. Eur. J. Immunol. (2002) [Pubmed]
  23. CCL19 induces rapid dendritic extension of murine dendritic cells. Yanagawa, Y., Onoé, K. Blood (2002) [Pubmed]
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