CCL18  (趋化因子 CCL18)

CCL18，又称巨噬细胞炎症蛋白-4 (MIP-4)，肺和激活调节趋化因子(PARC)、树突状细胞 (DC)-趋化因子 1 (DC-CK1) 和替代巨噬细胞激活相关 CC 趋化因子-1 (AMAC-1)，是一种 CC 趋化因子家族的小细胞因子。CCL18 在人类基因中位于 17 号染色体上，与 CCL3 具有最多的氨基酸同一性 (65%)，编码长为 89 个氨基酸的蛋白质，在 N' 末端还有一个 20 个氨基酸长的肽信号序列，可以发出其分泌信号，在内质网中被切割成一个 69 个氨基酸长的成熟蛋白质^[1]。CCL18 主要由先天免疫系统的抗原呈递细胞产生，包括树突状细胞、单核细胞和巨噬细胞，而在T 细胞和B 细胞中不会产生。在巨噬细胞中，CCL18 由 Th2 细胞因子 IL-4 和 IL-13 诱导，它们编程巨噬细胞分化为 AAM。而 AAMs 有助于急性炎症反应的愈合阶段以及慢性炎症性疾病的组织重塑和纤维化。CCL18 可以与 PITPNM3、GPR30 和 CCR8 受体结合，其中 CCL18 与 CCR8 的结合会诱导 Th2 细胞的趋化性。此外，CCL18 也可以作为中性 CCR3 拮抗剂，参与炎症反应。有研究表明，CCL18 及其受体 CCR8 在活动性嗜酸性粒细胞炎症期间在人类患病组织中共表达。与此同时，在多种疾病中，包括各种恶性肿瘤和炎症性关节、肺部和皮肤疾病中已证实 CCL18 的产生增强^[2]。

CCL18, also known as macrophage inflammatory protein-4 (MIP-4), pulmonary and activation-regulated chemokine (PARC), dendritic cell (DC)-chemokine 1 (DC-CK1) and alternative macrophage activation-associated CC chemokine-1 (AMAC-1), is a small cell factor of the CC chemokine family. CCL18 is located on chromosome 17 in the human gene and has the highest amino acid identity (65%) with CCL3, encoding an 89 amino acid long protein with a 20 amino acid long peptide signal sequence at the N' terminus that signals its secretion and is cleaved in the endoplasmic reticulum into a 69 amino acid long mature protein^[1]. CCL18 is mainly produced by antigen-presenting cells of the innate immune system, including dendritic cells, monocytes and macrophages, but not in T and B cells. In macrophages, CCL18 is induced by the Th2 cytokines IL-4 and IL-13, which program macrophages to differentiate into AAMs, which contribute to the healing phase of acute inflammatory responses and to tissue remodeling and fibrosis in chronic inflammatory diseases.CCL18 can bind to PITPNM3, GPR30, and CCR8 receptors, where CCL18 binding to CCR8 binding induces chemotaxis of Th2 cells. In addition, CCL18 can also act as a neutral CCR3 antagonist and participate in the inflammatory response. It has been shown that CCL18 and its receptor CCR8 are co-expressed in diseased human tissues during active eosinophilic inflammation. In parallel, enhanced production of CCL18 has been demonstrated in a variety of diseases, including various malignancies and inflammatory joint, lung and skin diseases^[2].

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