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

Group 2 innate lymphoid cells (ILC2s) have been found to take part in type 2 inflammation by secreting T_H2 cytokines. Apolipoprotein A-I (Apo-AI), a major structural and functional protein of high-density lipoproteins, has anti-inflammatory effects on neutrophils, monocytes, macrophages, and eosinophils. However, its effects on ILC2s are not well characterized.

We aimed to investigate the effect of Apo-AI on the proliferation and function of ILC2s as well as its possible mechanism.

The protein expression of Apo-AI and the percentage of ILC2s in peripheral blood between 20 allergic rhinitis patients and 20 controls were detected by ELISA and flow cytometry. The effect of Apo-AI and miR-155 on ILC2 proliferation and function was detected by tritiated thymidine incorporation and ELISA. Anima models were adopted to verify the effect of Apo-AI in vivo.

Elevated expression of Apo-AI was observed in allergic rhinitis patients. Apo-AI promotes ABCA1 expression by ILC2s, which can be inhibited by anti-Apo-AI. Apo-AI decreased ILC2 proliferation and the microRNA levels of GATA3 and RORα from ILC2s. The miR-155 overexpression promoted the upregulation of GATA3 and type II cytokines from ILC2s, while the addition of Apo-AI or miR-155 inhibitor significantly inhibited expression of GATA3 and type II cytokines by ILC2s. 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.

Apo-AI suppressed the proliferation and function of ILC2s through miR-155 in allergic rhinitis. Our data provide new insights into the mechanism of allergen-induced airway inflammation.