A proinflammatory role for interleukin-22 in the immune response to hepatitis B virus.
A proinflammatory role for interleukin-22 in the immune response to hepatitis B virus.
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DOI：
10.1053/j.gastro.2011.06.051
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发表时间：
2011-11
期刊：
影响因子：
29.4
通讯作者：
Robek MD
中科院分区：
文献类型：
--
作者：
Zhang Y;Cobleigh MA;Lian JQ;Huang CX;Booth CJ;Bai XF;Robek MD
分泌白细胞介素（IL）-22的T辅助（Th）17细胞在肝脏和其他组织中具有免疫调节和保护特性。IL-22诱导促炎基因的表达，但在肝细胞中也是促有丝分裂和抗凋亡的。因此，它可能具有多种功能的免疫应答B型肝炎病毒（HBV）。我们研究了IL-22在HBV转基因小鼠中调节肝脏炎症的作用，并测量了HBV感染患者中IL-22的水平。在HBV转基因小鼠中，注射单剂量的IL-22增加了促炎基因的肝脏表达，但不直接抑制病毒复制。当HBV免疫小鼠的脾细胞被转移到HBV转基因小鼠，随后的肝损伤的严重程度得到改善的IL-22的中和。在该模型中，IL-22耗竭不影响干扰素-γ介导的HBV特异性细胞毒性T细胞启动的病毒复制的非致细胞病变抑制，但显著抑制抗原非特异性炎症细胞向肝脏的募集。急性HBV感染患者外周血Th 17细胞比例和血清IL-22浓度明显升高。IL-22似乎是肝脏中T细胞识别HBV后炎症反应的重要介质。这些研究结果可能与开发基于麻黄碱的HBV感染患者治疗方法有关。
T-helper (Th)17 cells that secrete interleukin (IL)-22 have immunomodulatory and protective properties in the liver and other tissues. IL-22 induces expression of proinflammatory genes, but is also mitogenic and anti-apoptotic in hepatocytes. Therefore, it could have multiple functions in the immune response to hepatitis B virus (HBV). We examined the role of IL-22 in regulating liver inflammation in HBV transgenic mice and measured levels of IL-22 in HBV-infected patients. In HBV transgenic mice, injection of a single dose of IL-22 increased hepatic expression of proinflammatory genes, but did not directly inhibit virus replication. When splenocytes from HBV-immunized mice were transferred into HBV transgenic mice, the severity of the subsequent liver damage was ameliorated by neutralization of IL-22. In this model, IL-22 depletion did not affect interferon-γ–mediated noncytopathic inhibition of virus replication initiated by HBV-specific cytotoxic T cells, but it significantly inhibited recruitment of antigen–non-specific inflammatory cells into the liver. In patients with acute HBV infections, the percentage of Th17 cells in peripheral blood and concentration of IL-22 in serum were significantly increased. IL-22 appears to be an important mediator of the inflammatory response following recognition of HBV by T cells in the liver. These findings might be relevant to the development of cytokine-based therapies for patients with HBV infection.
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