Requirement for interleukin-1 to drive brain inflammation reveals tissue-specific mechanisms of innate immunity.
Requirement for interleukin-1 to drive brain inflammation reveals tissue-specific mechanisms of innate immunity.
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DOI：
10.1002/eji.201444748
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发表时间：
2015-02
影响因子：
5.4
通讯作者：
Allan, Stuart M.
中科院分区：
文献类型：
--
作者：
Giles, James A.;Greenhalgh, Andrew D.;Davies, Claire L.;Denes, Adam;Shaw, Tovah;Coutts, Graham;Rothwell, Nancy J.;McColl, Barry W.;Allan, Stuart M.
免疫系统与影响大脑的多种疾病有关，因此是一个有吸引力的治疗目标。白细胞介素-1 (IL-1) 是先天免疫系统的有效调节剂，对于宿主防御非常重要，但也与大脑损伤和疾病有关。在这里，我们证明 IL-1 是驱动小鼠大脑对炎症挑战的先天免疫反应的关键介质，但在包括肺和腹膜在内的脑外组织中是可有可无的。我们还证明 IL-1α 是导致 CNS 对 IL-1 依赖的重要配体，而源自 CNS 区室（最有可能是小胶质细胞）的 IL-1 是驱动这种效应的主要来源。这些数据揭示了以前未知的 IL-1 在驱动先天免疫方面的组织特异性要求，并表明可以选择性地靶向 IL-1 介导的大脑炎症，而不会损害对抵抗感染很重要的全身先天免疫反应。这种特性可用于减轻大脑中与损伤和疾病相关的炎症，而不增加对全身感染的易感性，全身感染是几种神经系统疾病的重要并发症。
The immune system is implicated in a wide range of disorders affecting the brain and is, therefore, an attractive target for therapy. Interleukin-1 (IL-1) is a potent regulator of the innate immune system important for host defense but is also associated with injury and disease in the brain. Here, we show that IL-1 is a key mediator driving an innate immune response to inflammatory challenge in the mouse brain but is dispensable in extracerebral tissues including the lung and peritoneum. We also demonstrate that IL-1α is an important ligand contributing to the CNS dependence on IL-1 and that IL-1 derived from the CNS compartment (most likely microglia) is the major source driving this effect. These data reveal previously unknown tissue-specific requirements for IL-1 in driving innate immunity and suggest that IL-1-mediated inflammation in the brain could be selectively targeted without compromising systemic innate immune responses that are important for resistance to infection. This property could be exploited to mitigate injury- and disease-associated inflammation in the brain without increasing susceptibility to systemic infection, an important complication in several neurological disorders.
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DOI：
10.1086/656365
发表时间：
2010-10-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Perrone LA;Szretter KJ;Katz JM;Mizgerd JP;Tumpey TM
通讯作者：
Tumpey TM
Interleukin-1家族：回到未来。
影响因子：
32.4
作者：
Garlanda C;Dinarello CA;Mantovani A
通讯作者：
Mantovani A
影响因子：
5.3
作者：
McColl, Barry W.;Rothwell, Nancy J.;Allan, Stuart M.
通讯作者：
Allan, Stuart M.
影响因子：
82.9
作者：
Chen, Chun-Jen;Kono, Hajime;Rock, Kenneth L.
通讯作者：
Rock, Kenneth L.
影响因子：
3
作者：
Tanabe, M;Matsumoto, T;Yamaguchi, K
通讯作者：
Yamaguchi, K