Type I interferons inhibit maturation and activation of mouse Langerhans cells
Type I interferons inhibit maturation and activation of mouse Langerhans cells
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DOI：
10.1111/j.0022-202x.2005.23803.x
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发表时间：
2005-07-01
影响因子：
6.5
通讯作者：
Tamaki, K
中科院分区：
文献类型：
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作者：
Fujita, H;Asahina, A;Tamaki, K
I型干扰素（IFN）在抗病毒防御中具有重要作用，并且它们在病毒感染后在多种细胞中产生。已知IFN-α/β处理未成熟树突状细胞（DC）诱导其表型和功能成熟，但仍不清楚该细胞因子家族的刺激是否影响朗格汉斯细胞（LC）的功能和成熟。我们使用直接从BALB/c小鼠皮肤分离的高度富集（> 95%）LC，并将LC与脾脏CD 11 c（+）DC进行比较，从而解决了这一问题。I型IFN处理的LC表现出产生IL-12和炎性细胞因子IL-6和TNF-α的能力受损，而IL-10的产生没有增加。在脾DC中，炎性细胞因子的产生通过I型IFN治疗而增强。关于趋化因子，在LC和脾DC中，I型IFN上调炎性趋化因子如CXCL 10、CXCL 11、CCL 3、CCL 4和CCL 5的产生。引人注目的是，IFN-β处理降低了LC上CD 40、CD 54、CD 80和CD 86的表达，而IFN-β处理的脾DC显示这些分子的表达增强。此外，IFN-β处理的LC具有抗CD 3诱导的T细胞增殖的共刺激活性受损。最后，用IFN-α/β处理降低了LC向CCL 21的迁移能力。这些结果表明，I型IFN以直接方式抑制LC的成熟和活化。我们的观察结果可能提供一个新的解释报告不能LC作为有效的抗原呈递细胞在皮肤和粘膜病毒感染。
Type I interferons (IFN) have an essential role in antiviral defense, and they are produced upon viral infection In a variety of cells. IFN-alpha/beta treatment of immature dendritic cells (DC) is known to induce their phenotypic and functional maturation, but it remains unclear whether stimulation by this cytokine family influences the functions and maturation of Langerhans cells (LC). We used highly enriched (> 95%) LC directly isolated from BALB/c mouse skin and addressed this issue, comparing LC with splenic CD11c(+) DC. Type I IFN-treated LC exhibited impaired ability to produce IL-12 and inflammatory cytokines, IL-6 and TNF-alpha, whereas IL-10 production was not augmented. In splenic DC, the production of inflammatory cytokines was rather enhanced by type I IFN treatment. With regard to chemokines, in both LC and splenic DC, type I IFN upregulated the production of inflammatory chemokines, such as CXCL10, CXCL11, CCL3, CCL4, and CCL5. Strikingly, IFN-beta treatment reduced the expression of CD40, CD54, CD80, and CD86 on LC, whereas IFN-beta-treated splenic DC showed enhanced expression of these molecules. Furthermore, IFN-beta-treated LC had impaired costimulatory activity for anti-CD3-induced proliferation of T cells. Finally, treatment with IFN-alpha/beta reduced the migratory capacity of LC to CCL21. These results indicate that type I IFN inhibit maturation and activation of LC in a direct manner. Our observations may provide a novel explanation for the reported inability of LC to act as potent antigen-presenting cells in cutaneous and mucosal viral infection.