circS100A11 regulates PKD1-mediated food allergy through recruiting EIF4A3.

BACKGROUND: Food allergy is a potentially serious immune system reaction that significantly impacts the quality of life for individuals. Studies have shown that dysregulation of circular RNAs (circRNAs) mediates the activation of immune cells and inflammatory mechanisms in allergic diseases. This study aimed to elucidate its functions and the pathways involved in food allergic reactions. METHODS: A Th2-polarized food allergy model was established in BALB/c mice using ovalbumin (OVA) adsorbed to aluminum hydroxide. Allergic responses were evaluated using a combination of clinical scoring, histology (H&E), and transmission electron microscopy (TEM). Serum IgE and cytokines (IL-4, IL-5, IL-13) were measured by ELISA. Molecular expressions were analyzed by western blot and qRT-PCR. RNA immunoprecipitation (RIP) and PAR-CLIP assays validated RNA-protein interactions. RESULTS: circS100A11, EIF4A3, and PKD1 was upregulated in sensitized mice. EIF4A3 was found to bind to and stabilized PKD1 mRNA, and its overexpression exacerbated allergic reactions in a PKD1-dependent manner. circS100A11 was found to directly interact with EIF4A3, promoting the recruitment of EIF4A3 to the PKD1 transcript. circS100A11 knockdown alleviated allergy, which was reversed by EIF4A3 overexpression. The detrimental effects of the circS100A11/EIF4A3 axis were abolished by concurrent PKD1 knockdown. CONCLUSION: Our findings define a novel regulatory pathway in which circS100A11 aggravates food allergy by recruiting EIF4A3 to enhance PKD1 expression, presenting a potential therapeutic target for intervention.