LncRNA AK085865 depletion ameliorates asthmatic airway inflammation by modulating macrophage polarization.

• Mice deficient in AK085865 are protected from Der f1-induced allergic airway inflammation. • AK085865 deletion in M2 macrophages is the major cause of decreased susceptibility of AA induced by Der f1. • The percentage of ILC2s is reduced in AK085865−/− mice, possibly due to a decrease in the number of M2 macrophages. • Knockout of AK085865 in M2 macrophages has no significant effect on promoting ILCP differentiation into ILC2s. • M2 macrophages promote the differentiation of ILCP into ILC2s, probably through the exosomal pathway. 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. [ABSTRACT FROM AUTHOR]