Interleukin-22 but not interleukin-17 provides protection to Hepatocytes during acute liver inflammation
Interleukin-22 but not interleukin-17 provides protection to Hepatocytes during acute liver inflammation
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DOI：
10.1016/j.immuni.2007.07.023
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发表时间：
2007-10-01
期刊：
影响因子：
32.4
通讯作者：
Flavell, Richard A.
中科院分区：
文献类型：
--
作者：
Zenewicz, Lauren A.;Yancopoulos, George D.;Flavell, Richard A.
细胞因子白介素 22 (IL-22) 主要由辅助性 T 细胞 17 (Th17) CD4(+) T 细胞表达，在慢性炎症性疾病期间高度上调。 IL-22 受体表达在免疫细胞上不存在，而是仅限于组织，提供从免疫系统到组织的信号传导方向。然而，IL-22 在炎症反应中的作用已被表明促炎和抗炎功能的数据所混淆。在此，我们提供的证据表明，在炎症过程中，IL-22 在预防组织损伤方面发挥了保护作用。 IL-22 缺陷小鼠的肝细胞对与肝炎相关的有害免疫反应高度敏感。此外，表达 IL-22 的 Th17 细胞在 IL-22 缺陷小鼠的肝炎期间提供保护。另一方面，白介素 17 (IL-17) 与 IL-22 共表达，可以诱导类似的细胞反应，但在肝脏炎症中没有观察到作用。我们的数据表明，IL-22 作为一种保护性分子，可以抵消免疫反应的破坏性，从而限制组织损伤。
The cytokine interleukin-22 (IL-22) is primarily expressed by T helper 17 (Th17) CD4(+) T cells and is highly upregulated during chronic inflammatory diseases. IL-22 receptor expression is absent on immune cells, but is instead restricted to the tissues, providing signaling directionality from the immune system to the tissues. However, the role of IL-22 in inflammatory responses has been confounded by data suggesting both pro- and anti-inflammatory functions. Herein, we provide evidence that during inflammation, IL-22 played a protective role in preventing tissue injury. Hepatocytes from mice deficient in IL-22 were highly sensitive to the detrimental immune response associated with hepatitis. Additionally, IL-22-expressing Th17 cells provided protection during hepatitis in IL-22-deflcient mice. On the other hand, interleukin-17 (IL-17), which is coexpressed with IL-22 and can induce similar cellular responses, had no observable role in liver inflammation. Our data suggest that IL-22 serves as a protective molecule to counteract the destructive nature of the immune response to limit tissue damage.