Interleukin (IL)-18 promotes the development of chronic gastrointestinal helminth infection by downregulating IL-13.

Interleukin (IL)-18 promotes the development of chronic gastrointestinal helminth infection by downregulating IL-13.
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DOI:
10.1084/jem.194.3.355
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发表时间:
2001-08-06
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Grencis RK
Grencis RK
中科院分区:
其他
文献类型:
--
作者:
Helmby H;Takeda K;Akira S;Grencis RK

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胃肠道线虫小鼠鞭虫的排出由涉及白细胞介素(IL)-4和IL-13的辅助性T(Th)2型应答介导。在这里,我们表明,Th 1应答相关的易感性涉及IL-18和caspase-1的预先激活,然后是IL-12和干扰素(IFN)-γ在肠道中。IL-18缺陷小鼠对慢性T.小鼠感染和用重组(r)IL-18体内处理正常小鼠抑制IL-13和IL-4分泌,但不影响IFN-γ。体内处理T.用rIL-18感染IFN-γ缺陷小鼠,证实IL-18对IL-13分泌的抑制作用不依赖于IFN-γ。因此,IL-18在慢性T.小鼠感染,而是作为Th 2细胞因子的直接调节剂。这些结果首次证明了IL-18在胃肠道线虫感染过程中调节Th细胞反应的关键作用。
Expulsion of the gastrointestinal nematode Trichuris muris is mediated by a T helper (Th) 2 type response involving interleukin (IL)-4 and IL-13. Here we show that Th1 response–associated susceptibility involves prior activation of IL-18 and caspase-1 followed by IL-12 and interferon (IFN)-γ in the intestine. IL-18–deficient mice are highly resistant to chronic T. muris infection and in vivo treatment of normal mice with recombinant (r)IL-18 suppresses IL-13 and IL-4 secretion but does not affect IFN-γ. In vivo treatment of T. muris–infected IFN-γ–deficient mice with rIL-18 demonstrated that the inhibitory effect of IL-18 on IL-13 secretion is independent of IFN-γ. Hence, IL-18 does not function as an IFN-γ–inducing cytokine during chronic T. muris infection but rather as a direct regulator of Th2 cytokines. These results provide the first demonstration of the critical role of IL-18 in regulating Th cell responses during gastrointestinal nematode infection.
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影响因子: 4.4
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