IL-17 and IFN-gamma mediate the elicitation of contact hypersensitivity responses by different mechanisms and both are required for optimal responses.
IL-17 and IFN-gamma mediate the elicitation of contact hypersensitivity responses by different mechanisms and both are required for optimal responses.
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DOI：
10.4049/jimmunol.0804108
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发表时间：
2009-07-15
期刊：
影响因子：
--
通讯作者：
Xu H
中科院分区：
文献类型：
--
作者：
He D;Wu L;Kim HK;Li H;Elmets CA;Xu H
半抗原诱导的皮肤接触性超敏反应是一种延迟型细胞免疫反应，可由产生干扰素-γ或IL-17的CD8+T细胞介导。然而，这些细胞因子诱导CHS的机制仍未完全阐明。在这里，我们显示，与野生型对照相比，在干扰素-γ受体−/−或IL-17R−/−小鼠中，过继转移半抗原激活的野生型CD8+T细胞的CHS减少。IL-17R−/−受者经半抗原刺激后，皮肤中粒细胞和巨噬细胞的浸润明显减少，而γ-−/−受体受者虽然CD8+T细胞的浸润均受到抑制，但对其影响较小。相反，在干扰素-γ受体−/−中，反应性氧化物种的活性受到显著抑制，但在IL-17R−/−接受者中受影响较小。进一步的分析表明，与野生型对照相比，干扰素-γ受体−/−或IL-17R−/−受体的半抗原攻击皮肤中趋化因子和细胞因子的表达受到不同的调节。有趣的是，在皮肤内注射重组IL-17会引起炎症，并伴有高水平的白细胞渗透，而注射干扰素-γ则会引起炎症，并产生高水平的活性氧化物种。此外，中和IL-17RγR−/−或IL-17Rγ中的IL-17进一步抑制半抗原诱导的野生型−/−+T细胞过继转移CHS。研究表明，干扰素-γ和IL-17通过不同的机制介导CHS的诱导，并且这两种细胞因子都是最佳反应所必需的。这一结果提高了对发病机制的理解，并为CHS的治疗策略提供了新的见解。
Hapten induced contact hypersensitivity (CHS) in the skin is a delayed type cellular immune response which can be mediated by CD8+ T cells that produce IFN-γ or IL-17. However, mechanisms for these cytokines in the elicitation of CHS remain to be fully elucidated. Here we show that adoptive transfer of CHS with hapten primed wild type CD8+ T cells is reduced in IFN-γR−/− or IL-17R−/− mice compared to wild type controls. The infiltration of granulocytes and macrophages in the hapten challenged skin of IL-17R−/− recipients is significantly reduced whereas it is less affected in IFN-γR−/− recipients although CD8+ T cell infiltration is inhibited in both recipients. In contrast, the activity of reactive oxidative species is significantly inhibited in IFN-γR−/− but is less affected in IL-17R−/− recipients. Further analysis reveals that the expression of chemokines and cytokines is differentially regulated in the hapten challenged skin of IFN-γR−/− or IL-17R−/− recipients compared to wild type controls. Interestingly, injection of recombinant IL-17 in the skin induces inflammation with a high level of leukocyte infiltration whereas injection of IFN-γ induces inflammation with a high level of reactive oxidative species. Moreover, neutralization of IL-17 in IFN-γR−/− or IFN-γ in IL-17R−/− mice further suppresses the adoptive transfer of CHS by hapten primed wild type CD8+ T cells. The study demonstrates that IFN-γ and IL-17 mediate the elicitation of CHS by different mechanisms and that both cytokines are required for optimal responses. This outcome improves understanding of pathogenesis and provides new insights into therapeutic strategies for CHS.
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影响因子：
5.5
作者：
Engeman, T;Gorbachev, AV;Fairchid, RL
通讯作者：
Fairchid, RL
DOI：
10.1073/pnas.95.14.8233
发表时间：
1998-07-07
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
14.2
作者：
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通讯作者：
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影响因子：
30.5
作者：
Hsu, Hui-Chen;Yang, PingAr;Mountz, John D.
通讯作者：
Mountz, John D.