Gamma-ray irradiation impairs dendritic cell migration to CCL19 by down-regulation of CCR7 and induction of cell apoptosis.

Gamma-ray irradiation impairs dendritic cell migration to CCL19 by down-regulation of CCR7 and induction of cell apoptosis.
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伽马射线照射通过下调 CCR7 和诱导细胞凋亡来损害树突状细胞向 CCL19 的迁移

DOI:
10.7150/ijbs.7.168
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发表时间:
2011-02-14
影响因子:
9.2
通讯作者:
Cai J
Cai J
中科院分区:
生物学2区
文献类型:
--
作者:
Liu C;Lin J;Zhao L;Yang Y;Gao F;Li B;Cui J;Cai J

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树突状细胞(Dendritic cells,DCs)是最强的抗原提呈细胞,在免疫应答的调节中起着关键作用,其向次级淋巴组织的迁移在先天性免疫和获得性免疫的启动中也起着重要作用。放射治疗现在是某些类型癌症的常规治疗,超过20%的癌症患者在治疗过程中需要放射治疗。然而,电离辐射对DC迁移能力的影响在很大程度上是未知的。在本文中,我们报告了γ射线照射可以显著抑制LPS诱导的DC表达CCR7和产生PGE2的上调,从而在体外和体内抑制DC向CCL19的迁移。此外,γ射线暴露的DC也表现出凋亡率增加和细胞活力降低。此外,我们证明外源性PGE2可以部分减轻γ射线诱导的DC迁移障碍,并恢复CCR7的表达。我们的工作表明,γ射线照射在免疫应答过程中影响DC的功能,包括DC迁移,并且PGE 2通过控制CCR7的表达,是DC迁移的重要调节剂。
Dendritic cells (DCs) are the most potent antigen-presenting cells and play a crucial role in the regulation of immune response and migration of DCs into secondary lymphoid tissues also play an important role in the initiation of innate and adaptive immunity. Radiation therapy is now a routine treatment for certain types of cancer and over 20 percent of cancer patients will require radiation therapy during the treatment of their disease. However, the influence of ionizing irradiation on the migratory ability of DCs is largely unknown. In this article, we report that γ ray irradiation can significantly inhibit LPS-triggered up regulation of CCR7 expression and PGE2 production by DC, thus impairing DC migration towards CCL19 in vitro and in vivo. Moreover, γ ray exposed DC also displayed an increased apoptosis rate and decreased cell viability. Furthermore, we demonstrate that exogenous PGE2 can partly reduce the gamma-ray induced migratory impairment and restored CCR7 expression of DC. Our work suggests that γ irradiation affects DC function at multiple steps during the immune response including DC migration, and that PGE2, via control of CCR7 expression, is an important regulator of DC migration.
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