CCL22  (趋化因子 CCL22)

CCL22，又称巨噬细胞衍生趋化因子 (MDC)，一种 CC 趋化因子，在人类基因组中位于第 16 号染色体上，是一种由 CCL22 基因编码的蛋白质，在氨基酸水平上与 CCL17 具有 37% 的同一性。CCL22 由树突状细胞和巨噬细胞分泌，可被多种刺激因子上调，例如脂多糖，细胞因子。其中，Th2 细胞因子 IL-4 和 IL-13 可诱导骨髓细胞中 CCL22 的产生，并可被 Th1 细胞因子 IFN-γ 抑制。CCL22 除了可作为表达 CCR4 的 Th2 淋巴细胞、单核细胞、单核细胞衍生的树突细胞和自然杀伤细胞的有效趋化剂，也可以通过与趋化因子受体 CCR4 相互作用而对其靶细胞产生影响。CCL22 是 CCR4 内化的有效诱导剂，CCR4 的 CCL22 结合可以降低 CCR4 的后续功能反应。CCL22 与 CCR4 的相互作用涉及多种病理学，从过敏反应和自身免疫到肿瘤生长。而能够阻断 CCL17 和 CCL22 介导的 Th2 细胞和 Treg 细胞募集的小分子化合物和抗体已被证明在哮喘、特应性疾病和肿瘤生长的各种疾病模型中产生积极作用。此外，在过敏性气道炎症模型中显示 CCL22 及其受体在 TH2 淋巴细胞募集中的重要作用。也可以通过调节成熟胸腺细胞通过该器官的迁移来参与胸腺生成^[1][2]。

CCL22, also known as macrophage-derived chemokine (MDC), a CC chemokine located on chromosome 16 in the human genome, is a protein encoded by the CCL22 gene that shares 37% identity with CCL17 at the amino acid level. CCL22 is secreted by dendritic cells and macrophages and can be upregulated by a variety of stimulatory factors, such as lipopolysaccharides, cytokines. Among them, the Th2 cytokines IL-4 and IL-13 induce CCL22 production in myeloid cells and can be inhibited by the Th1 cytokine IFN-γ. In addition to acting as a potent chemotactic agent for CCR4-expressing Th2 lymphocytes, monocytes, monocyte-derived dendritic cells, and natural killer cells, CCL22 can also affect its target cells by interacting with the chemokine receptor CCR4. CCL22 is a potent inducer of CCR4 internalization, and CCL22 binding to CCR4 reduces the subsequent functional response of CCR4. The interaction of CCL22 with CCR4 is involved in a variety of pathologies, ranging from allergic reactions and autoimmunity to tumor growth. In contrast, small molecule compounds and antibodies capable of blocking CCL17 and CCL22-mediated recruitment of Th2 and Treg cells have been shown to have positive effects in various disease models of asthma, atopic disease and tumor growth. In addition, an important role of CCL22 and its receptors in TH2 lymphocyte recruitment has been shown in models of allergic airway inflammation. It can also be involved in thymopoiesis by regulating the migration of mature thymocytes through this organ^[1][2].

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