CCL18 – Beyond chemotaxis

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HighlightsCCL18 is constitutively expressed and up-regulated in diseases.CCL18 has a weak chemotactic activity toward multiple immune cells including Treg.CCL18 inhibits chemokine-related cell recruitment by binding to glycosaminoglycans.CCL18 gives immune cells a regulatory phenotype and function by direct activation.CCL18 has a pro-fibrotic and pro-neoplastic activity.The chemokine CCL18 is constitutively expressed in human lung and serum, and is further elevated during pathologic conditions such as allergy, fibrosis and cancer, suggesting that it may participate in both homeostatic and inflammatory processes. Under steady state conditions, CCL18 has chemotactic activity, albeit modest, toward naïve T cells and as such, may be involved in the initiation of the adaptive response. Its chemotactic effect on inflammatory cells is ambiguous as it attracts both regulatory and inflammatory immune cells. CCL18 can also modulate tissue inflammation by inhibiting cell recruitment through binding to glycosaminoglycans with high affinity, thereby displacing other chemokines bound to the endothelial surface. CCL18 induces regulatory phenotype and function of immune cells through direct activation and plays a major role in fibrotic processes, particularly in the lung. Finally, CCL18 is involved in cancer cell activation and migration and also participates in immune tolerance toward cancer. Its high constitutive expression levels and its further up-regulation in many diseases, together with its moderate chemoattractant properties support the fact that this chemokine has activities beyond cell recruitment.

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