Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institutes (Wannan Medical College), Wuhu, PR China; Central Laboratory, The First Affiliated Hospital of Wannan Medical College, Wuhu, PR China.
Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institutes (Wannan Medical College), Wuhu, PR China; Department of Laboratory Medicine (Wannan Medical College), Wuhu, PR China.
Int Immunopharmacol. 2020 Jun;83:106450. doi: 10.1016/j.intimp.2020.106450. Epub 2020 Apr 1.
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.
越来越多的证据表明，巨噬细胞极化的调节剂可能在过敏性哮喘 (AA) 的发展中发挥关键作用。然而，长链非编码 RNA (lncRNA) 在调节尘螨蛋白 1 (Der f1) 诱导的 AA 发病机制中巨噬细胞极化的确切作用尚不完全清楚。本研究旨在确定 lncRNA AK085865 在调节 AA 中巨噬细胞中的功能。在这里，我们报告 lncRNA AK085865 作为巨噬细胞极化的关键调节剂，可减轻哮喘气道炎症的病理进展。在 Der f1 的刺激下，AK085865 小鼠表现出减弱的过敏性气道炎症，包括 BALF 中的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 处理的 AK085865 小鼠显示出较少的 M2 巨噬细胞。在用 WT 小鼠的骨髓来源的巨噬细胞 (BMDM，M0) 进行处理后，Der f1 处理的 AK085865 小鼠也显示出较轻的炎症反应。我们进一步观察到 AK085865 哮喘小鼠中的 II 型先天淋巴样细胞 (ILC2) 比例下降。此外，M2 巨噬细胞有助于促进 ILC2 的分化，可能是通过 M2 巨噬细胞分泌的外体途径。总之，这些发现表明，AK085865 的耗竭可以通过调节巨噬细胞极化来改善哮喘气道炎症，并且 M2 巨噬细胞可以促进先天淋巴样细胞祖细胞 (ILCP) 向 ILC2 的分化。
