地塞米松调节T细胞免疫应答保护小鼠急性炎性肝损伤的作用

Dexamethasone Protects Mice against Acute Inflammatory Liver Injury by Regulating T Cell Immune Response

背景:在小鼠急性炎性肝损伤中,地塞米松(Dex)可通过抑制天然免疫细胞功能抑制肝损伤进展,然而T细胞是否参与此保护作用尚少见报道。目的:探讨Dex在急性炎性肝损伤中对T细胞免疫应答的调节效应。方法:6只雄性C57BL/6J小鼠随机分为实验组和模型组,在以脂多糖诱导急性炎性肝损伤模型前1 h,两组分别腹腔注射Dex5 mg/kg和等体积PBS。建模12 h后处死小鼠,行临床评分并检测肝功能;分离脾脏单个核细胞,分析T细胞活化情况以及各T细胞亚群的细胞因子表达、分泌和转录因子表达。结果:实验组小鼠临床评分和血清转氨酶水平均明显低于模型组,脾脏CD44+CD62L-T细胞(活化或记忆性T细胞)比率显著降低,Th1型细胞因子IFN-γ表达、分泌减少,Th2型细胞因子IL-4表达、分泌增加,调节性T细胞(Treg细胞)比率、Th2/Th1、Treg/Th1比值增加;同时,Th1细胞特异性转录因子表达下调,Th2、Treg细胞特异性转录因子表达上调。结论:Dex通过抑制T细胞活化并调节T细胞亚群分化(抑制Th1细胞分化,促进Th2、Treg细胞分化),在急性炎性肝损伤中起一定保护作用。

Background：Dexamethasone can protect mice against the acute inflammatory liver injury by inhibiting innate immune cell function. However,the roles of T cell in this protective effect remain unknown. Aims：To investigate the regulatory effect of dexamethasone on T cell immune response in acute inflammatory liver injury. Methods：Six male C57BL/ 6J mice were randomly divided into 2 groups. One hour before induction of acute inflammatory liver injury by lipopolysaccharide, dexamethasone 5 mg/ kg and PBS were given intraperitoneally in experimental group and model group,respectively. All the mice were sacrificed 12 hours after model construction. The clinical score and liver function parameters were assessed;splenic mononuclear cells were isolated for measurements of T cell activation,as well as cytokine expression,secretion, and transcriptional factor expression for different T-cell subsets. Results：Clinical score and serum levels of transaminase were significantly lower in experimental group when compared with the model group. Meanwhile,percentage of CD44 ＋CD62L - T cells（i. e. activated or memory T cells）from spleen was significantly decreased in experimental group. Among splenic T cell population,expression and secretion of IFN-γ,a Th1-type cytokine,was decreased;expression and secretion of IL-4,a Th2-type cytokine,percentage of regulatory T cells（Treg cells）,and ratios of Th2 / Th1 and Treg/ Th1 were increased;transcriptional factor specific for Th1 cells was down-regulated,and those for Th2 and Treg cells were up-regulated. Conclusions：Dexamethasone inhibits T cell activation and directs the reciprocal T cell lineage differentiation （repressing Th1 cell differentiation,promoting Th2 and Treg cell differentiation）,which may contribute to the protection against acute inflammatory liver injury.