MIP-3 beta/CCL19  (趋化因子 CCL19)

CCL19，又称 MIP-3 beta，是一种免疫稳态趋化因子，其在人类基因组中位于第 9 号染色体上。CCL19 在胸腺和淋巴结中大量表达，在气管和结肠中表达中等，在胃、小肠、肺、肾和脾中表达较低。CCL19 可以与趋化因子受体 CCR7 结合并发挥作用。CCR7 是第一个发现的具有七个跨膜α 螺旋的淋巴细胞特异性 G 蛋白偶联受体 (GPCR)。 CCR7 表达于双阴性和单阳性胸腺细胞，包括幼稚 T 细胞、中枢记忆 T 细胞、调节性 T 细胞、幼稚 B 细胞、半成熟/成熟 DC 和 NK 细胞，以及少数肿瘤细胞，它作为将稳态淋巴细胞引导至次级淋巴器官的关键调节因子。而 CCL19 是已知唯一能有效刺激 β-arrestin 介导的 CCR7 磷酸化和内化的趋化因子，导致受体脱敏和抗原 (Ag) 呈递 DC 迁移，从而影响 T 细胞反应。基于 CCL19-CCR7 的信号通路在组织免疫和炎症反应记忆发挥着重要的作用。此外，还在针对多种病毒的基于疫苗的保护中发挥作用，如 HIV-1 感染，丙型肝炎病毒（HCV），单纯疱疹病毒 1 (HSV-1)等。CCL19 和 CCR7 的相互作用也有助于免疫细胞释放抗病毒相关细胞因子（例如，IFN-γ 和 IL-4），从而促进 T 细胞增殖和 DC 对抗原的摄取^[1][2]。

CCL19, also known as MIP-3 beta, is an immunostable chemokine that is located on chromosome 9 in the human genome. CCL19 is abundantly expressed in the thymus and lymph nodes, moderately expressed in the trachea and colon, and less expressed in the stomach, small intestine, lung, kidney, and spleen. CCL19 binds to and functions as a chemokine receptor, CCR7. CCR7 is the first CCR7 is the first lymphocyte-specific G protein-coupled receptor (GPCR) identified with seven transmembrane alpha helices. CCR7 is expressed on both double-negative and single-positive thymocytes, including naive T cells, central memory T cells, regulatory T cells, naive B cells, semimature/mature DCs and NK cells, as well as a few tumor cells, where it serves as a key regulator for directing steady-state lymphocytes to secondary lymphoid organs. In contrast, CCL19 is the only chemokine known to effectively stimulate β-arrestin-mediated phosphorylation and internalization of CCR7, leading to receptor desensitization and migration of antigen (Ag)-presenting DCs, thereby affecting T cell responses. The CCL19-CCR7-based signaling pathway plays an important role in tissue immunity and inflammatory response memory. In addition, it also plays a role in vaccine-based protection against a variety of viruses, such as HIV-1 infection, hepatitis C virus (HCV), and herpes simplex virus 1 (HSV-1), etc. The interaction of CCL19 and CCR7 also contributes to the release of antiviral-associated cytokines (e.g., IFN-γ and IL-4) by immune cells, thereby promoting T cell proliferation and DC uptake of antigens^[1][2].

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