The role of autophagy regulated by the PI3K/AKT/mTOR pathway and innate lymphoid cells in eosinophilic chronic sinusitis with nasal polyps.

BACKGROUND: The PI3K/Akt/mTOR pathway and autophagy are important physiological processes. But their roles in eCRSwNP remains controversial. METHODS: In this study, we used the eCRSwNP mouse model, PI3K/Akt/mTOR pathway inhibitors, and autophagy inhibitors and activators to investigate the regulatory effects of the PI3K/Akt/mTOR pathway on autophagy, and their effects on eosinophilic inflammation, and tissue remodeling. The role of ILC2s in eCRSwNP was also studied, and the relationship between ILC2s and autophagy was preliminarily determined. RESULTS: Our results show that eosinophilic inflammation in eCRSwNP mice could be inhibited by promoting the autophagy; otherwise, eosinophilic inflammation could be promoted. Meanwhile, inhibition of the PI3K/Akt/mTOR pathway can further promote autophagy and inhibit eosinophilic inflammation. Meanwhile, inhibiting the PI3K/Akt/mTOR pathway and promoting autophagy can reduce the number of ILC2s and the severity of tissue remodeling in the nasal polyps of eCRSwNP mice. CONCLUSIONS: We conclude that the PI3K/Akt/mTOR pathway plays roles in eosinophilic inflammation and tissue remodeling of eCRSwNP, in part by regulating the level of autophagy. The downregulation of autophagy is a pathogenesis of eCRSwNP; therefore, the recovery of normal autophagy levels might be a new target for eCRSwNP therapy. Furthermore, autophagy might inhibit eosinophilic inflammation and tissue remodeling, in part by reducing the number of ILC2s.

Role of autophagy and mitophagy of group 2 innate lymphoid cells in allergic and local allergic rhinitis.

Background: Roles of ILC2s in allergic rhinitis (AR) and local allergic rhinitis (LAR) are unclear. In this study, we are determined to find the levels of autophagy and mitophagy of ILC2s in allergic nasal inflammation. Methods: ELISA was used to detect type 2 inflammatory cytokines. Hematoxylin and eosin (H&E) staining were used to compare the eosinophil (EOS) infiltration of nasal tissue specimens. Flow cytometry was used to detect the levels of ILC2s and Th2 cells. Immunohistochemistry (IHC) and Western blot (WB) were used to detect the levels of Beclin1, LC3, p62, PINK1, Parkin, FUNDC1, and BNIP3 in nasal mucosa. The levels of autophagy related proteins and mitophagy related proteins of the ILC2s were detected by WB. The number of autophagosomes of ILC2s was observed by transmission electron microscopy. The co-localization levels of GFP-LC3 and Mito tracker in ILC2s were observed by confocal microscopy using immunofluorescence. Results: We found that the level of type 2 inflammation in AR and LAR mice was significantly increased. The levels of autophagy and mitophagy of AR and LAR mice in nasal mucosa and ILC2s were both increased. Conclusions: ILC2s may be associated with the occurrence and development of nasal allergic inflammation. The abnormal increase of autophagy and mitophagy levels in the nose may be associated with the incidence of AR and LAR. Abnormal autophagy and mitophagy levels of ILC2s cells may be one of the causes of allergic nasal inflammation.