RORα overexpression reduced interleukin-33 expression and prevented mast cell degranulation and inflammation by inducing autophagy in allergic rhinitis

Background: Retinoid acid receptor related orphan receptor alpha (ROR alpha) is a nuclear receptor that along with other bioactive factors regulates cell proliferation, differentiation, and immunomodulation in vivo.Aims: The objective of this study was to explore the function and mechanism of ROR alpha in allergic rhinitis (AR).Materials and MethodsDerp1 was used to construct an AR cell model in HNEpC cells, and ROR alpha was overexpressed or silenced in the AR HNEpC cells. Next, LAD2 cells were co-cultured with the Derp1-treated HNEpC cells. Additionally, an AR mouse model was established using by OVA, and a ROR alpha Adenovirus was delivered by nebulizing. Pathological tissue structures were evaluated by hematoxylin-eosin staining, and the levels of ROR alpha, interleukin-33 (IL-33), and other proteins were analyzed immunohistochemistry, western blotting, and immunofluorescence staining. IL-33, IL-4, IL-5, and IL-13 levels were detected using enzyme-linked immunosorbent assay kits and cell migration was assessed by Transwell assays.Results: Our data showed that ROR alpha was downregulated in the nasal mucosa tissues of AR patients. Derp1 treatment could cause a downregulation of ROR alpha, upregulation of IL-33, the induction of NLRP3 inflammasomes, and cell migration in HNEpC cells. Furthermore, ROR alpha overexpression dramatically attenuated IL-33 levels, NLRP3 inflammasome activity, and the migration of AR HNEpC cells induced with Derp1. Moreover, ROR alpha in AR HNEpC cells could prevent mast cell (MC) degranulation and inflammation by accelerating autophagy, ROR alpha overexpression inhibited MC degranulation and NLRP3-induced inflammation in the AR model mice. ROR alpha overexpression reduced IL-33 expression in nasal epithelial cells, and also suppressed MC degranulation and inflammation by promoting autophagy.Conclusion: ROR alpha inhibits NLRP3 inflammasome in HNEpC, and attenuated mast cells degranulation and inflammation through autophagy in AR.

Automated summary

According to the research findings, ROR alpha plays an important inhibitory role in allergic rhinitis, alleviating mast cell degranulation and inflammation by suppressing NLRP3 inflammasome and promoting autophagy.