CCL21

What is CCL21 protein?

CCL21 (C-C motif chemokine ligand 21) gene is a protein coding gene which situated on the short arm of chromosome 9 at locus 9p13. This antimicrobial gene is one of several CC cytokine genes clustered on the p-arm of chromosome 9. Cytokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. The CC cytokines are proteins characterized by two adjacent cysteines. The CCL21 protein is consisted of 134 amino acids and its molecular mass is approximately 14.6 kDa.

What is the function of CCL21 protein?

Similar to other chemokines the protein encoded by this gene inhibits hemopoiesis and stimulates chemotaxis. This protein is chemotactic in vitro for thymocytes and activated T cells, but not for B cells, macrophages, or neutrophils. The cytokine encoded by CCL21 gene may also play a role in mediating homing of lymphocytes to secondary lymphoid organs. It is a high affinity functional ligand for chemokine receptor 7 that is expressed on T and B lymphocytes and a known receptor for another member of the cytokine family (small inducible cytokine A19).

Fig1. Biological functions of CCL21/CCR7 axis. (Le Han, 2023)

CCL21 Related Signaling Pathway

The signaling pathway of CCL21 involves the CCR7 signaling pathway, which regulates cell migration and survival mainly through the activation of PI3K/Akt, MAPK and NF-κB. In addition, CCL21 can chemotactic T cells, B lymphocytes, mature dendritic cells (DC) and NK cells, and participate in the homing process of lymphocytes. In addition, tumor cells secrete immunosuppressive factors such as CCL21 to block the host's anti-tumor immune response, thus achieving immune escape.

CCL21 Related Diseases

It has attracted much attention because of its important role in immune cell migration and inflammation regulation. Diseases associated with CCL21 include inflammatory diseases, autoimmune diseases, and tumors, and its secretion in some aggressive tumor cells may promote tumor development.

Bioapplications of CCL21

Some relevant studies have explored its potential role in cancer treatment, including improving the effectiveness of immunotherapy by modulating the activity of immune cells in the tumor microenvironment, and there are also studies trying to exploit the biological role of CCL21 to develop new drugs or therapies targeting immunotherapy.

Case study 1: C Y Hong, 2014

The potential use of lymphoid chemokines to generate a dendritic cell (DC) cancer vaccine is not yet clear. The researchers investigated the effect of lymphoid chemokines on DC function and on the production of effective cytotoxic T lymphocytes (CTLs) for application of cancer vaccine using monocyte-derived mature DCs (mDCs) prestimulated with lymphoid chemokines.

mDCs exposed to a secondary lymphoid organ chemokine (SLC/CCL21) dramatically induced CTL response by increasing cytolytic activity without any significant alterations on expression of cell surface markers. mDCs prestimulated with CCL21 showed higher levels of CXCL10 (IP-10) production, but not the production of CCL22, compared with untreated mDCs. IP-10 treatment during CTL generation with DCs dramatically enhanced tumour-specific CTL response compared with untreated CTLs, and these enhanced CTL-inducing functions of CCL21-treated DCs were inhibited by anti-IP-10 treatment.

Fig1. Enhanced cytotoxicity of CTLs by CCL21-treated αDC1s. The increased number of IFNγ-secreting cells in CCL21-treated αDC1s.

Fig2. The dramatic enhancement of the MART-1+/CD8+ T cell population in CTLs stimulated by CCL21-treated αDC1s with or without IP-10 addition.

Case study 2: Sarah R Pickens, 2012

To determine the role of CCL21 and its receptor CCR7 in the pathogenesis of rheumatoid arthritis (RA). The role of CCL21 and/or CCR7 in angiogenesis was examined using in vitro chemotaxis, tube formation, and in vivo Matrigel plug assays. Finally, the mechanism by which CCL21 mediates angiogenesis was determined by Western blot analysis and endothelial cell chemotaxis and tube formation assays.

CCL21, but not CCL19, at concentrations present in the RA joint, induced human microvascular endothelial cell (HMVEC) migration that was mediated through CCR7 ligation. Suppression of the phosphatidylinositol 3-kinase pathway markedly reduced CCL21-induced HMVEC chemotaxis and tube formation. Neutralization of either CCL21 in RA synovial fluid or CCR7 in HMVECs significantly reduced the induction of HMVEC migration and/or tube formation by RA synovial fluid.

Fig3. CCL21-induced HMVEC chemotaxis showed that CCL21 induced cell migration.

Fig4. CCL21-induced HMVEC migration and tube formation are supressed by PI3K inhibition.

CCL21 has several biochemical functions, for example, CCR chemokine receptor binding,CCR7 chemokine receptor binding,chemokine activity. Some of the functions are cooperated with other proteins, some of the functions could acted by CCL21 itself. We selected most functions CCL21 had, and list some proteins which have the same functions with CCL21. You can find most of the proteins on our site.

CCL21 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with CCL21 here. Most of them are supplied by our site. Hope this information will be useful for your research of CCL21.

LRRK1;LRRK2;a41_vaccw;CCR7;GOT2;q81ue9_bacan;UBQLN4