Department of Internal Medicine and Clinical Nutrition, Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Department of Internal Medicine and Clinical Nutrition, Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
J Allergy Clin Immunol. 2017 Mar;139(3):1007-1016.e9. doi: 10.1016/j.jaci.2016.06.035. Epub 2016 Aug 1.
Allergic airway inflammation is triggered by allergen exposure through several steps including release of IL-33, which promotes cytokine (IL-5, IL-13) production by type 2 innate lymphoid cells (ILC2s). MicroRNA (miR)-155 has recently been described to regulate adaptive responses in allergic inflammation. However, the role of miR-155 in the regulation of ILC2s remains unexplored.
We sought to elucidate the contribution of miR-155 in ILC2 expansion using experimental murine models of allergic airway inflammation.
To determine the role of miR-155 in the regulation of ILC2s in allergic airway inflammation, miR-155 deficient (miR-155) and wild-type (WT) mice were subjected to acute or chronic allergen-induced inflammation or treated with recombinant IL-33.
miR-155 was 10-fold upregulated in WT-derived ILC2s in response to IL-33. Furthermore, miR-155 mice demonstrated impaired lung IL-33 levels in response to allergen challenge and the number of ILC2s was significantly reduced in allergen-challenged miR-155 mice compared with WT mice. Exogenous IL-33 treatment revealed that miR-155 is needed for IL-33-induced ILC2 expansion and eosinophilic airway inflammation. Indeed, ILC2s from IL-33-challenged miR-155 lungs exhibited impaired proliferation, GATA-3 expression, and IL-13 production as compared with IL-33-challenged WT ILC2s.
Our findings for the first time demonstrate that ILC2s and IL-33 signaling are regulated by miR-155 in allergic airway inflammation.
过敏性气道炎症是由过敏原暴露引发的，包括通过几种步骤释放白细胞介素 33（IL-33），从而促进 2 型先天淋巴样细胞（ILC2）产生细胞因子（IL-5、IL-13）。微 RNA（miR）-155 最近被描述为调节过敏性炎症中的适应性反应。然而，miR-155 在调节 ILC2 中的作用仍未得到探索。
我们旨在通过过敏性气道炎症的实验性小鼠模型阐明 miR-155 在 ILC2 扩增中的作用。
为了确定 miR-155 在过敏性气道炎症中对 ILC2 调节的作用，使用 miR-155 缺陷型（miR-155）和野生型（WT）小鼠进行急性或慢性变应原诱导的炎症，或用重组 IL-33 进行处理。
在对 IL-33 的反应中，WT 来源的 ILC2 中的 miR-155 上调了 10 倍。此外，在变应原挑战时，miR-155 小鼠的肺 IL-33 水平受损，并且与 WT 小鼠相比，变应原挑战的 miR-155 小鼠中的 ILC2 数量明显减少。外源性 IL-33 处理表明，miR-155 是 IL-33 诱导的 ILC2 扩增和嗜酸性气道炎症所必需的。事实上，与 IL-33 挑战的 WT ILC2 相比，来自 IL-33 挑战的 miR-155 肺部的 ILC2 表现出增殖、GATA-3 表达和 IL-13 产生受损。
我们的研究结果首次表明，在过敏性气道炎症中，ILC2 和 IL-33 信号受 miR-155 调节。
