Apolipoprotein A-I inhibited group II innate lymphoid cell response mediated by microRNA-155 in allergic rhinitis

Abstract

BackgroundGroup 2 innate lymphoid cells (ILC2s) have been found to take part in type 2 inflammation by secreting Th2 cytokines. Apolipoprotein A-I (Apo-AI), a major structural and functional protein of high-density lipoproteins, plays anti-inflammatory effects on neutrophils, monocytes, macrophages and eosinophils. However, its effects on ILC2 are not well characterized. ObjectiveIn this study, we aimed to investigate to the effect of Apo-AI on the proliferation and function of ILC2 as well as possible mechanism. MethodsThe protein expression of Apo-AI and the percentage of ILC2 in peripheral blood between 20 AR and 20 controls were detected using enzyme-linked immunosorbnent assay (ELISA) and flow cytometry. The effect of Apo-AI and miR-155 on ILC2 proliferation and function were detected by tritiated thymidine incorporation and ELISA. Anima models were adopted to verify the effect of Apo-AI in vivo. ResultsElevated expression of Apo-AI was observed in AR patients. The Apo-AI promotes ABCA1 expression by ILC2, which can be inhibited by anti-Apo-AI. The Apo-AI decreased ILC2 proliferation and the mRNA levels of GATA3 and RORα from ILC2. The miR-155 over-expression promoted the up-regulation of GATA-3 and type II cytokines from ILC2, while the addition of Apo-AI or miR-155 inhibitor inhibited the expression of GATA-3 and type II cytokines by ILC2 significantly. Apo-AI-/- mice showed as enhanced allergen-induced airway inflammation. The miR-155 inhibitor can reverse the enhanced allergen-induced airway inflammation in Apo-AI-/- mice, while miR-155 mimics can reverse the decreased allergen-induced airway inflammation in Apo-AI treated mice. ConclusionApo-AI suppressed the proliferation and function of ILC2 through miR-155 in AR. Our data provided new insights into the mechanism of allergen-induced airway inflammation.