Type II innate lymphoid cells (ILC2) play a very important role in the pathogenesis of allergic asthma. This study aims to investigate whether miR-146a inhibition of asthma is related with interleukin (IL)-33 signaling path way in ILC2 and the underlying mechanisms. Asthma mice model was induced by ovalbumin. miRNA146a mimics was administrated to asthma mice or transfected to activated ILC2 purified from asthma mice lung. RT-PCR was used to detect miRNA146a level in lung tissue and ILC2. IL-5 and IL-13 levels in culture supernatant were detected by flow cytometry. Interleukin-1 receptor-associated kinase 1 (IRAK1), TNF receptor-associated factor 6 (TRAF6), signal transducer and activator of transcription 1 (STAT1) protein expression levels were detected by western blot. miR-146a directly inhibited ILC2 function and suppressed ILC2 proliferation both in vivo and in vitro. During stimulation of ILC2, miR-146a expression gradually increased with a decrease of cell proliferation. Modulation of ILC2 function by miR-146a may depend on IL-33/interleukin 1 receptor-like 1 (IL1RL1 or ST2) signaling through inhibiting IRAK1 and TRAF6.miR-146a can inhibit IRAK1 and TRAF6, downstream molecules of ST2 signal pathway, thereby negatively regulate IL-33/ST2-activated ILC2 to inhibit asthma. Targeting miR-146 maybe a novel strategy for the treatment of allergic asthma.

中文翻译：

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MicroRNA-146a通过抑制IRAK1和TRAF6负调控激活的第2组先天淋巴样细胞中的IL-33。

II型先天淋巴样细胞（ILC2）在过敏性哮喘的发病机理中起着非常重要的作用。本研究旨在探讨miR-146a对哮喘的抑制作用是否与ILC2中的白介素（IL）-33信号通路有关，并探讨其潜在机制。卵清蛋白诱导哮喘小鼠模型。将miRNA146a模拟物给予哮喘小鼠或转染至从哮喘小鼠肺中纯化的活化ILC2。RT-PCR用于检测肺组织和ILC2中的miRNA146a水平。通过流式细胞术检测培养上清液中的IL-5和IL-13水平。Western blot检测白细胞介素1受体相关激酶1（IRAK1），TNF受体相关因子6（TRAF6），信号转导子和转录激活因子1（STAT1）的蛋白表达水平。miR-146a在体内和体外直接抑制ILC2功能并抑制ILC2增殖。在刺激ILC2的过程中，miR-146a的表达随着细胞增殖的减少而逐渐增加。miR-146a对ILC2功能的调节可能依赖于IL-33 /白介素1受体样1（IL1RL1或ST2）的信号传导，通过抑制IRAK1和TRAF6来实现.miR-146a可以抑制IR2和TRAF6，即ST2信号通路的下游分子，从而负调节IL-33 / ST2激活的ILC2抑制哮喘。靶向miR-146可能是一种治疗过敏性哮喘的新策略。miR-146a对ILC2功能的调节可能依赖于IL-33 /白介素1受体样1（IL1RL1或ST2）的信号传导，通过抑制IRAK1和TRAF6来实现.miR-146a可以抑制IR2和TRAF6，即ST2信号通路的下游分子，从而负调节IL-33 / ST2激活的ILC2抑制哮喘。靶向miR-146可能是一种治疗过敏性哮喘的新策略。miR-146a对ILC2功能的调节可能依赖于IL-33 /白介素1受体样1（IL1RL1或ST2）的信号传导，通过抑制IRAK1和TRAF6来实现.miR-146a可以抑制IR2和TRAF6，即ST2信号通路的下游分子，从而负调节IL-33 / ST2激活的ILC2抑制哮喘。靶向miR-146可能是一种治疗过敏性哮喘的新策略。