MicroRNA-155 is a critical regulator of type 2 innate lymphoid cells and IL-33 signaling in experimental models of allergic airway inflammation
MicroRNA-155 is a critical regulator of type 2 innate lymphoid cells and IL-33 signaling in experimental models of allergic airway inflammation
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DOI：
10.1016/j.jaci.2016.06.035
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发表时间：
2017-03-01
影响因子：
14.2
通讯作者：
Radinger, Madeleine
中科院分区：
文献类型：
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作者：
Johansson, Kristina;Malmhall, Carina;Radinger, Madeleine
背景：过敏性呼吸道炎症是由过敏原暴露引起的，包括释放IL-33，促进2型固有淋巴细胞(ILC2s)产生细胞因子(IL-5、IL-13)。MicroRNA(MiR)-155最近被描述为调节变态反应性炎症的适应性反应。目的：通过建立小鼠过敏性气道炎模型，探讨miR-155在ILC2扩张中的作用。方法：采用miR-155基因缺陷(miR-155 2/2)和野生型(WT)小鼠造成急、慢性变应原诱导的炎症反应或重组IL-33治疗，探讨miR-155在ILC2调节中的作用。结果：在WT来源的ILC2中，miR-155表达上调10倍。此外，miR-155 2/2小鼠表现出对变应原攻击的肺IL-33水平受损，并且与WT小鼠相比，变应原攻击miR-155 2/2小鼠的ILC2数量显著减少。外源性IL-33治疗显示，miR-155是IL-33诱导的ILC2扩张和嗜酸性气道炎所必需的。事实上，与IL-33攻击的WTILC2相比，IL-33攻击的miR-155 2/2肺的ILC2表现出增殖、GATA-3表达和IL-13产生的损害。结论：我们的发现首次证实了ILC2和IL-33信号在过敏性气道炎症中受到miR-155的调节。
Background: 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.Objective: We sought to elucidate the contribution of miR-155 in ILC2 expansion using experimental murine models of allergic airway inflammation.Methods: To determine the role of miR-155 in the regulation of ILC2s in allergic airway inflammation, miR-155 deficient (miR-155 2/2) and wild-type (WT) mice were subjected to acute or chronic allergen-induced inflammation or treated with recombinant IL-33.Results: miR-155 was 10-fold upregulated in WT-derived ILC2s in response to IL-33. Furthermore, miR-155 2/2 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 2/2 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 2/2 lungs exhibited impaired proliferation, GATA-3 expression, and IL-13 production as compared with IL-33-challengedWTILC2s.Conclusions: Our findings for the first time demonstrate that ILC2s and IL-33 signaling are regulated by miR-155 in allergic airway inflammation.