CCL18

Chemokine (C-C motif) ligand 18 (CCL18) is a small

CCL18 is produced and secreted mainly by innate immune system, and has effects mainly on the adaptive immune system. 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).

Gene and protein structure

The gene of CCL18 is most similar to

Sources

CCL18 is produced mainly by

The production of CCL18 is induced by T-helper 2 type cytokines, namely IL-4 and IL-13. Coupled with the fact that CCL18 is highly expressed in patients with allergic asthma[18] and other hypersensitivity diseases,^[6] CCL18 seems to play an important role for generating and maintaining a T-helper 2 (Th2) type response. Furthermore, the addition of CCL18 as an adjuvant for a malaria vaccine have shown efficacy, perhaps by recruiting immune cells to the site of vaccination.^[19] Finally, CCL18 is expressed by dendritic cells in the germinal center of inflamed lymph nodes, and recruits naïve B-cells for antigen presentation.^[20] Perhaps aberrant CCL18 expression is involved in the generation of chronic Th2 response, leading to asthma or arthritis.

Immunosuppression

In addition to immune-activating effects, CCL18 also has strong immunosuppressive effects. CCL18 induces immature dendritic cells to differentiate into an immunosuppressive dendritic cell that is capable producing CCL18 which attract T-cells, suppressing effector T-cell function, and generating T-regulatory cells by secreting large amounts of IL-10.^[10][21] Furthermore, exposure to CCL18 by macrophages causes them to mature in the #M2 spectrum, which promotes immunosuppression and healing.^[9]

Involvement in disease

Aberrant CCL18 expression is observed in many diseases, and it is thought that these abnormal expression patterns play a key role in these diseases.^[6] This table shows a list of all the diseases that CCL18 is involved in.

Breast cancer

The most understood disease that CCL18 is involved in is in breast cancer, where CCL18 induces metastasis of breast cancer cells by binding to PITPNM3.^[15] Perhaps CCL18, in breast cancers, is acting as an immunosuppressive cytokine by generating T-regulatory cells, generating immunosuppressive dendritic cells and macrophages, and recruiting effector T-cells to these dendritic cells and macrophages to abolish their anti-cancer functions and allowing the cancer to escape the immune system.

Autoimmunity and hypersensitivity

CCL18 is highly expressed in T-helper 2 mediated