抽象的
Background工作场所暴露于低分子量(LMW)剂(例如甲苯2,4-二异氰酸酯(TDI))引起的职业哮喘会给患者和社会带来重大负担。对于TDI诱导的哮喘中的先天淋巴样细胞(ILC)知之甚少。ILC功能的关键调节剂是MicroRNA-155,这是一种与哮喘相关的microRNA。
客观的确定TDI暴露是否会改变肺中的ILC数量,以及MicroRNA-155是否有助于TDI诱导的气道炎症和反应性过高。
方法C57BL/6 wild-type and microRNA-155 knockout mice were sensitised and challenged with TDI or vehicle. Intracellular cytokine expression in ILC and T cells was evaluated in bronchoalveolar lavage fluid (BAL) by flow cytometry. Peribronchial eosinophilia and goblet cells were evaluated on lung tissue and airway hyperresponsiveness was measured with the forced oscillation technique. Putative ILC2 cells were identified in bronchial biopsies of subjects with TDI-induced occupational asthma using immunohistochemistry. Human bronchial epithelial cells were exposed to TDI or vehicle.
结果TDI-exposed mice had higher numbers of airway goblet cells, BAL eosinophils, CD4+T cells and ILC, with a predominant type 2 response and tended to have airway hyperresponsiveness. In TDI-exposed microRNA-155 knockout mice, inflammation and airway hyperresponsiveness was attenuated. TDI exposure induced IL-33 expression in human bronchial epithelial cells and in murine lungs, which was microRNA-155 dependent in mice. GATA3+CD3−cells, presumably ILC2, were present in bronchial biopsies.
结论TDI暴露与ILC数量增加有关。促炎的microRNA-155在TDI哮喘的鼠模型中至关重要,这表明它参与了由于LMW药物而引起的职业哮喘发病机理。
脚注
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利益冲突:Blomme博士报告了研究期间,来自根特大学的赠款的法兰德斯科学研究基金会的赠款。
Conflict of interest: Dr. Provoost has nothing to disclose.
利益冲突:范·埃克霍特(Van Eeckhoutte)博士没有什么可披露的。
利益冲突:Mirjam Roffel没有什么可披露的。
Conflict of interest: Dr. Pollaris has nothing to disclose.
Conflict of interest: Annelies Bontinck has nothing to disclose.
利益冲突:Vandenbroucke博士没有什么可披露的。
Conflict of interest: Dr. Verhamme has nothing to disclose.
利益冲突:Joos博士报告了阿斯利康(Astrazeneca)的赠款和个人费用,拜耳(Bayer)的个人费用,基西(Chiesi)的赠款,欧里卡(Eureca)的个人费用,glaxosmithkline的赠款和个人费用,来自Teva的个人费用,在提交工作之外的Teva;所有付款都是向他的雇主付款。
Conflict of interest: Dr. Cosio has nothing to disclose.
利益冲突:Vanoirbeek博士没有什么可披露的。
Conflict of interest: Dr. Brusselle has nothing to disclose.
Conflict of interest: Dr. Maes reports grants from Ghent University, grants from Fund for Scientific Research in Flanders, during the conduct of the study; personal fees from GlaxoSmithKline, outside the submitted work; and is shareholder of Oryzon Genomics and of Mendelion Lifesciences SL.
利益冲突:Bazzan博士没有什么可披露的。
利益冲突:Bonato博士没有什么可披露的。
Conflict of interest: Dr. Saetta reports grants from Laboratori Guidotti SpA, grants from Chiesi Farmaceutici SpA, outside the submitted work.
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- 已收到June 28, 2019.
- AcceptedMay 10, 2020.
- 复制right ©ERS 2020