Cxcl17

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 (see below chemokines).

In the CC chemokines, the cysteines follow each other directly, in the CXC chemokines they are separated by 1, in the CXXXC chemokines by 3 other amino acids. Chemokines are produced and secreted by a large number of immune cells. They mediate their signals by means of specific chemokine receptors via G-proteins. The fact that chemokines and their receptors are not only expressed on inflammatory cells, but also by epithelial cells, mesenchymal cells, neurogenic cells, endothelial cells, and various tumor cell lines, suggests that they participate in numerous regulatory cell functions.

CXCL17, also known as C-X-C motif chemokine 17 CXCL17 or VEGF co-regulated chemokine 1 (acronym= VCC-1), is encoded by the CXCL17 gene, a gene located on chromosome 19 in humans.

CXCL17 acts as a chemoattractant for monocytes, macrophages and dendritic cells. CXCL17 plays a role in the establishment of tumor-associated angiogenesis.

Primarily, CXCL17 is expressed in the mucosa of the lung parenchyma. The chemokine is considered an important regulator of an inflammatory mucosal reaction. However, CXCL17 is also expressed ectopically by keratinocytes and various tumor cell lines.

Inflammatory skin reactions: Activated keratinocytes are able to express CXCL17. Relevant CXCL17 mRNA levels are detected in psoriatic skin, but not in lesional atopic skin or in cutaneous T-cell lymphomas.

CXCL17 and malignancies: CXCL17 is expressed by a number of tumors and induces tumor progression by recruitment of myeloid-derived suppressor cells (MDSCs). Thus CXCL17 is produced and secreted in excessive amounts in colon cancer cells. The production of CXCL17 chemokines was highly superior to that of the chemokines CXCL10, CXCL9 and CCL2, which were also highly expressed. Also in hepatocellular carcinoma, overexpression of CXCL17, combined with an inflammatory tumor infiltrate, is correlated with a poor prognosis.

1. Burkhardt AM et al (2014) CXCL17 is a major chemotactic factor for lung macrophages. J Immunol 193:1468-1474.
2. Ohlsson L et al (2016) Ectopic expression of the chemokine CXCL17 in colon cancer cells. Br J Cancer 114:697-703.
3. Li L et al (2014) CXCL17 expression predicts poor prognosis and correlates with adverse immune infiltration in hepatocellular carcinoma. PLoS One 9:e110064.
4. Oka T et al (2017) CXCL17 Attenuates Imiquimod-Induced Psoriasis-like Skin Inflammation by Recruiting Myeloid-Derived Suppressor Cells and Regulatory T Cells. J Immunol pii: 1601607.