LncRNA AK085865 depletion ameliorates asthmatic airway inflammation by modulating macrophage polarization
LncRNA AK085865 depletion ameliorates asthmatic airway inflammation by modulating macrophage polarization
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LncRNA AK085865 耗竭通过调节巨噬细胞极化改善哮喘气道炎症
DOI：
10.1016/j.intimp.2020.106450
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发表时间：
2020-06-01
影响因子：
5.6
通讯作者：
Lv, Kun
中科院分区：
文献类型：
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作者：
Pei, Weiya;Zhang, Yingying;Lv, Kun
越来越多的证据表明，巨噬细胞极化调节可能在过敏性哮喘(AA)的发生发展中起关键作用。然而，在粉尘螨蛋白1(Der F1)诱导的再生障碍性贫血(AA)中，长非编码RNA(LncRNAs)在巨噬细胞极化调节中的确切作用尚不完全清楚。本研究旨在探讨lncRNA AK085865在再生障碍性贫血中对巨噬细胞的调节作用。在此，我们报道了lncRNA AK085865作为巨噬细胞极化的关键调节因子，减缓了哮喘气道炎症的病理进程。作为对Der F1攻击的反应，AK085865(-/-)小鼠的过敏性气道炎症减轻，包括BALF中嗜酸性粒细胞减少和IgE产生减少，这与粘液腺减少和杯状细胞增生有关。此外，与WT哮喘小鼠相比，Der F1治疗的AK085865(-/-)小鼠显示更少的M2巨噬细胞。采用WT小鼠骨髓来源的巨噬细胞(BMDM，M0)后，Der F1处理的AK085865(-/-)小鼠也表现出轻微的炎症反应。我们进一步观察到AK085865(-/-)哮喘小鼠的II型天然免疫淋巴样细胞(ILC2s)百分比降低。此外，M2巨噬细胞可能通过M2巨噬细胞分泌的胞外途径促进ILC2s分化。提示AK085865耗竭可通过调节巨噬细胞极化减轻哮喘气道炎症，M2巨噬细胞可促进先天淋巴祖细胞(ILCP)向ILC2分化。
Accumulating evidence indicates that regulators of macrophages polarization may play a key role in the development of allergic asthma (AA). However, the exact role of long non-coding RNAs (lncRNAs) in regulating in macrophages polarization in the pathogenesis of dermatophagoides farinae protein 1(Der f1)-induced AA is not fully understood. The purpose of this study was to determine the function of lncRNA AK085865 in regulating macrophages in AA. Here we report that lncRNA AK085865 served as a critical regulator of macrophages polarization and reduced the pathological progress of asthmatic airway inflammation. In response to the challenge of Der f1, AK085865(-/-) mice displayed attenuated allergic airway inflammation, including decreased eosinophil in BALF and reduced production of IgE, which were associated with decreased mucous glands and goblet cell hyperplasia. In addition, Der f1-treated AK085865(-/-) mice show fewer M2 macrophages when compared with WT asthmatic mice. After adopting bone marrow-derived macrophages (BMDM, M0) from WT mice, Der f1-treated AK085865(-/-) mice also revealed a light inflammatory reactions. We further observed that the percentage of type II innate immune lymphoid cells (ILC2s) decreased in AK085865(-/-) asthmatic mice. Moreover, M2 macrophages helped promote the differentiation of ILC2s, probably through the exosomal pathway secreted by M2 macrophages. Taken together, these findings reveal that AK085865 depletion can ameliorate asthmatic airway inflammation by modulating macrophage polarization and M2 macrophages can promote the differentiation of innate lymphoid cells progenitor (ILCP) into ILC2s.