Innate immune processes are sufficient for driving silicosis in mice
Innate immune processes are sufficient for driving silicosis in mice
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DOI：
10.1189/jlb.0210108
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发表时间：
2010-09-01
影响因子：
5.5
通讯作者：
Holian, Andrij
中科院分区：
文献类型：
--
作者：
Beamer, Celine A.;Migliaccio, Christopher T.;Holian, Andrij
肺部经常暴露于潜在的致病颗粒和微生物。最近已经变得明显的是，不仅先天免疫应答，而且对颗粒物（例如进入呼吸道的SiO2）的适应性免疫应答是复杂的动态事件。尽管矽肺发生的细胞机制和解剖学结果已被广泛研究，但仍知之甚少。基于它们的免疫调节能力，淋巴细胞可能在SiO2对环境挑战的呼吸反应中发挥关键作用。本研究的目的是表征SiO2暴露对呼吸免疫过程的影响，特别强调评估淋巴细胞在小鼠矽肺模型中的重要性。因此，使用淋巴细胞减少小鼠，包括NK缺陷型、Rag 1（-/-）或组合（Rag 1（-/-）NK缺失型），并证明SiO2诱导的纤维化和炎症可独立于T、B、NK T和NK细胞发生。在Rag 1（-/-）小鼠中的研究进一步表明，淋巴细胞可能通过调节Nalp 3炎性体参与SiO2诱导的炎症的调节。这一观察结果可能在治疗难治性或对当前疗法反应不佳的炎性和纤维化肺病方面具有临床意义。J. Leukoc. 88：547-557; 2010.
The lung is constantly exposed to potentially pathogenic particles and microorganisms. It has become evident recently that not only innate but also adaptive immune responses to particulates, such as SiO2 entering the respiratory tract, are complex and dynamic events. Although the cellular mechanisms and anatomical consequences involved in the development of silicosis have been studied extensively, they still remain poorly understood. Based on their capacity for immune regulation, lymphocytes may play a key role in the respiratory response to environmental challenge by SiO2. The objective of this study was to characterize the impact of SiO2 exposure on respiratory immune processes, with particular emphasis on evaluating the importance of lymphocytes in the murine silicosis model. Therefore, lymphopenic mice, including NK-deficient, Rag1(-/-), or a combination (Rag1(-/-) NK-depleted), were used and demonstrated that SiO2-induced fibrosis and inflammation can occur independently of T, B, NK T, and NK cells. Studies in Rag1(-/-) mice suggest further that lymphocytes may participate in the regulation of SiO2-induced inflammation through modulation of the Nalp3 inflammasome. This observation may have clinical relevance in the treatment of inflammatory and fibrotic lung diseases that are refractory or respond suboptimally to current therapeutics. J. Leukoc. Biol. 88: 547-557; 2010.