Interferon-inducible immunity-related GTPase Irgm1 regulates IFN gamma-dependent host defense, lymphocyte survival and autophagy.

Interferon-inducible immunity-related GTPase Irgm1 regulates IFN gamma-dependent host defense, lymphocyte survival and autophagy.
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DOI:
10.4161/auto.5.2.7445
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发表时间:
2009-02
期刊:
影响因子:
13.3
通讯作者:
Sher A
Sher A
中科院分区:
生物学1区
文献类型:
--
作者:
Feng CG;Zheng L;Lenardo MJ;Sher A

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IFN-γ 是一种多效细胞因子,在宿主抵抗中发挥关键作用,但如果调节不当,可能会对宿主有害。干扰素诱导免疫相关 GTP 酶家族 M 成员 1 (Irgm1) 先前被描述为巨噬细胞杀菌活性所需的效应分子,最近已被证明在调节 IFN-γ 依赖性细胞存活和宿主抵抗力方面发挥着先前未被认识的作用。 Irgm1 通过保护成熟效应 CD4+ T 淋巴细胞免受 IFN-γ 诱导的自噬性细胞死亡来调节它们的扩增/存活。重要的是,同时缺乏 IFN-γ 和 Irgm1 的小鼠可以避免单个 Irgm1−/− 动物在接触病原体后出现的淋巴细胞耗竭和死亡率增加的情况。我们认为,Irgm1 通过保护这些细胞免受自噬依赖性细胞死亡,在宿主 IFN-γ 应答期间维持 T 淋巴细胞稳态中发挥重要作用。
IFN-γ is a pleiotropic cytokine that plays a key role in host resistance yet when not properly regulated can become host-detrimental. The interferon-inducible Immunity Related GTPase family M member 1 (Irgm1), previously characterized as an effector molecule required for macrophage microbicidal activity, has been shown recently to play a previously unrecognized role in regulating IFN-γ-dependent cell survival and host resistance. Irgm1 regulates the expansion / survival of mature effector CD4+ T lymphocytes by protecting them from IFN-γ induced autophagic cell death. Importantly, mice deficient in both IFN-γ and Irgm1 were rescued from the lymphocyte depletion and increased mortality that occurs in single Irgm1−/− animals following pathogen exposure. We propose that Irgm1 plays a major role in maintaining T lymphocyte homeostasis during host IFN-γ responses by protecting these cells from autophagy-dependent cell death.
DOI: 10.1084/jem.20061303
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影响因子: --
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免疫相关的GTPase IRGM1通过防止干扰素γ诱导的细胞死亡促进活化的CD4+ T细胞群体的扩张。
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