Tim-3在调控IFI44表达及影响H1N1感染中的作用研究

Role of Tim-3 signal in regulating the expression of IFI44 and in H1N1 infection

目的探讨Tim-3信号影响免疫细胞抗感染作用的机制。方法通过基因芯片筛选及体内外验证的方法探讨Tim-3对IFI44(一种抗感染关键效应分子)表达的影响,并结合H1N1感染模型对其意义进行评价。结果在巨噬细胞上敲低Tim-3表达或通过Tim-3融合蛋白阻断Tim-3信号,均能显著提高IFI44的表达,而在Tim-3高表达的巨噬细胞中IFI44的表达受到明显抑制。在整体水平上检测Tim-3信号对IFI44表达的影响发现,给予受H1N1病毒感染小鼠腹腔注射s Tim-3蛋白能显著提高小鼠体内IFI44的表达进而降低H1N1病毒载量。结论 Tim-3在抑制抗病毒感染效应分子IFI44表达中发挥关键作用;部分解释了Tim-3调控抗感染免疫的机制,也为防治H1N1等病毒的感染提供了新的思路。

Reports showed that Tim-3, an immune regulator, is involved in the negative regulation ofanti-infection immunity. However, the mechanism and significance of this regulating process remain unclear. Thisstudy conducted to further explore the mechanisms by which Tim-3 regulates immune response in infection. Basedon microarray data, we investigate the influence of Tim-3 signal on the expression of IFI44, a key molecular inanti-infection immunity, in vitro and in vivo. We also evaluated the role of Tim-3 in H1N1 infection by blockingTim-3 pathway in vivo. Data showed that IFI44 expression was significantly elevated when Tim-3 was silenced orblocked by Tim-3 protein in cultured macrophage, while overexpression of Tim-3 lead to IFI44 expression decreasein macrophage. In H1N1 infected mouse, blockade of Tim-3 pathway using soluble Tim-3 significantly increasedIFI44 expression and decreased H1N1 virus load. We concluded that Tim-3 plays an essential role in inhibiting IFI44 and in regulating anti-virus immunity in vivo. This study sheds new light on the mechanisms Tim-3 regulatingimmune response and provides new strategy for the intervention of virus infection.