CCL18

Chemokine (C-C motif) ligand 18 (CCL18) is a small cytokine belonging to the CC chemokine family. It was previously known as Pulmonary and activation-regulated chemokine (PARC), dendritic cell (DC)-chemokine 1 (DC-CK1), alternative macrophage activation-associated CC chemokine-1 (AMAC-1), and macrophage inflammatory protein-4 (MIP-4). The effector functions that CCL18 exerts on the immune system is mainly on the adaptive immune system, while being produced and secreted mainly by innate immune system. Although the functions of CCL18 have been well studied in vitro, physiological effects of CCL18 in vivo have been difficult to characterize because there is no murine analog of CCL18. Only recently has the receptor for CCL18 been identified, and further characterization of CCL18 interactions with its receptor will lead to better understanding of the physiological role of CCL18 in humans.

Gene and protein structure

The gene of CCL18 is most similar to CCL3. CCL18 is located on Chromosome 17, along with many other macrophage inflammatory proteins (MIP). The gene itself has 3 exons and 2 introns; but, unlike other chemokines, CCL18 includes 2 pseudo-exons (exons that do not appear in the final peptide) in the first intron. Because of these pseudo-exons, it is believed that CCL18 arose as a result of a gene fusion event between CCL3-like protein encoding genes and gained a different function over time due to accumulating mutations. CCL18 is a 89 peptide-long protein, with a 20 peptide signalling sequence (to signal its secretion) at the N’ terminus which is cleaved in the endoplasmic reticulum into a 69 peptide mature protein.