Protective effect of Th22 cells and intrahepatic IL-22 in drug induced hepatocellular injury
Protective effect of Th22 cells and intrahepatic IL-22 in drug induced hepatocellular injury
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Th22细胞和肝内IL-22在药物诱导的肝细胞损伤中的保护作用。
DOI：
10.1016/j.jhep.2015.02.004
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发表时间：
2015-07-01
影响因子：
25.7
通讯作者：
Xie, Qing
中科院分区：
文献类型：
--
作者：
Lai, Rongtao;Xiang, Xiaogang;Xie, Qing
背景和目标：Th 22细胞调节宿主免疫抵抗病原体入侵，包括保护宿主免受慢性B型肝炎的侵害，但药物性肝损伤（DILI）与Th 22/Th 17细胞的关系尚不清楚。我们研究了Th 22细胞在DILI发展中的作用。方法：检测了DILI、非DILI肝病和健康对照者外周血Th 22/Th 17/Th 1细胞的频率和肝内IL-22/IL-17的产生。在第0周（定义为7天内发生肝损伤）、第4周和第24周测定DILI患者的血浆IL-22/IL-17和相关细胞因子。结果：DILI发作组Th 22/Th 17细胞比例明显高于HC组（P < 0. 05），而HC组Th 22/Th 17细胞比例明显高于HC组（P < 0. 05）。肝细胞损伤型DILI患者Th 22细胞及相关细胞因子水平明显升高。肝内IL-22水平与肝再生呈正相关。DILI患者肝功能改善后血浆IL-22水平明显高于肝功能未改善者。多因素分析显示，治疗4周时血浆IL-22水平的比值比（OR）为1.054 [95%可信区间（CI）为1.012，1.124]。Th 22及其相关细胞因子可能具有保肝作用，这为深入了解DILI的免疫发病机制提供了新的视角。血浆IL-22可能是判断DILI预后的可靠指标，并为DILI的治疗提供新的靶点。(C)2015年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background & Aims: Th22 cells regulate host immunity against pathogenic invasion, including protecting host against chronic hepatitis B; however, the relationship between drug induced liver injury (DILI) and Th22/Th17 cells is still unclear. We investigated the role of Th22 cells in DILI development.Methods: The frequencies of peripheral Th22/Th17/Th1 cells and intrahepatic IL-22/IL-17 production from DILI, non-DILI liver diseases, and healthy controls were examined. Plasma IL-22/IL-17 and the related cytokines were determined in DILI patients at week 0 (defined as the occurrence of liver injury within 7 days), 4 and 24. Multivariable stepwise logistic regression was applied to explore the associations between various factors and recovery of DILI.Results: The frequencies of Th22/Th17 cells were significantly higher in DILI onset patients than HC. Significant increase of Th22 cells and the related cytokines levels was observed in DILI with hepatocellular injury type. There was a positive correlation between intrahepatic IL-22 level and liver regeneration. Plasma IL-22 level was higher in DILI patients with improved liver function than unimproved function. Multivariable analysis showed that the odds ratio (OR) of plasma IL-22 at 4 weeks was 1.054 [95% confidence interval (CI), 1.012, 1.124].Conclusions: Increased peripheral and intrahepatic IL-22-secreting cells are detected in DILI. Th22 and its related cytokines might be hepato-protective, which might provide new perspective for understanding the immunopathogenesis of DILI. Plasma IL-22 might be a reliable indicator to evaluate the prognosis of DILI and provide a novel therapeutic target for DILI treatment. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.