Ccl20

Chemokines, a subgroup of cytokines, are small (size between 8 and 10 kDa), chemotactically active proteins (signal proteins). They are common in all vertebrates, some virus types and bacteria. In humans, about 50 chemokines are currently known. A strongly conserved structural feature of all chemokines is a fixed group of cysteine residues that is stabilized by 1 or 2 disulfide bridges. This key structural position in the molecule is responsible for its fixed 3-dimensional structure.

In the CC chemokines, the cysteines follow each other directly (see figure), in the CXC chemokines they are separated (CC = acronym for cysteine-cysteine) by 1, in the CXXXC chemokines by 3 other amino acids. We show that CCL15 is processed in human synovial fluid by matrix metalloproteinases (MMPs) and serine proteases. They transmit their signals by binding to chemokine receptors via G-proteins. Some chemokines have a pro-inflammatory effect, others have a regulatory effect on the formation, homeostasis and proliferation of tissues.

CCL20, also known as C-C motif chemokine ligand 20, or "B-lymphocyte surface antigen B1" is a small, human cytokine belonging to the CC chemokine family. The chemokine is encoded by the CCL20 gene on chromosome 2.

CCL20 binds largely exclusively to the chemokine receptor CCR6. Recently, it has been shown that beta-defensins can also bind to CCR6 receptors. CCL6 has intense chemotactic effects on lymphocytes and dendritic cells and to a lesser extent on neutrophilic granulocytes, but not on monocytes.

CCL20 is produced in numerous organs, including peripheral lymphocytes, lymph nodes, liver, thymus, testes, prostate, and intestine.

Activation of the CCL20 gene can occur by microbial factors such as lipopolysaccharides (LPS) as well as inflammatory cytokines such as TNF-alpha and interferon gamma. Interleukin-10 leads to inhibition of CCL20 chemokine expression.

CCL20 is involved in homoestasis and bacterial defense (demonstrated in Escherichia coli and Staphylococcus aureus) of mucosa-associated lymphoid tissue by attracting lymphocytes and dendritic cells to epithelial cells.

Diseases in which CCL20 plays a pathogenetic role:

In Crohn's disease, CCL20 production is markedly increased in intestinal epithelia. Here, TNF-alpha markedly activates CCL20 production in intestinal epithelial cells. In contrast, TGF-beta1 inhibits CCL20 production.

Pancreatic cancer: CCL20 is upregulated in the parenchyma of pancreatic cancer (C25.9). This involves both tumor epithelia and "tumor-associated macrophages - TAMs). A role of the chemokine in migration and metastasis of the tumor is assumed.

Lung cancer: In non-small cell lung cancer (NSCLC - C34.9), CCL20 is upregulated by interleukin-beta stimulated autosecretion, leading to tumor cell migration and proliferation through activation of the ERK and PI3K signaling pathways.

Cutaneous T-cell lymphoma: In cutaneous T-cell lymphoma, the CCL20/CCR6 axis is also upregulated. This overexpression appears to correlate with the proliferative capacity of the lymphoma.

CCL20 regulates sperm motility and chemotaxis by binding to the CCR6 receptor.

Cigarette smoking: CCL20, like several other chemokines, is upregulated in the lungs of smokers.

1. Ikeda S et al (2016) Disruption of CCL20-CCR6 interaction inhibits metastasis of advanced cutaneous T-cell lymphoma. Oncotarget 7:13563-13574.
2. Lee AY et al (2015) The relationship between CCR6 and its binding partners: does the CCR6-CCL20 axis have to be extended? Cytokines 72:97-101.
3. Liu B et al (2016) Tumor-associated macrophage-derived CCL20 enhances the growth and metastasis of pancreatic cancer. Acta Biochim Biophys Sin (Shanghai) 48:1067-1074.
4. Marafini I et al (2017) CCL20 Is Negatively Regulated by TGF-β1 in Intestinal Epithelial Cells and Reduced in Crohn's Disease Patients With a Successful Response to Mongersen, a Smad7 Antisense Oligonucleotides. J Crohn's colitis 11:603-609.
5. Marafini I et al (2016) CCL20 Is Negatively Regulated by TGF-β1 in Intestinal Epithelial Cells and Reduced in Crohn's Disease Patients With a Successful Response to Mongersen, a Smad7 Antisense Oligonucleotides. J Crohn's colitis pii: jjw191.
6. Wang GZ et al (2015) Tobacco smoke induces production of chemokine CCL20 to promote lung cancer. Cancer Lett 363:60-70.
7. Wang B et al (2016) Production of CCL20 from lung cancer cells induces the cell migration and proliferation through PI3K pathway. J Cell Mol Med 20:920-929.