MicroRNA-155 is a critical regulator of type 2 innate lymphoid cells and IL-33 signaling in experimental models of allergic airway inflammation

Abstract

Background: Allergic airway inflammation is triggered by allergen exposure through several steps including release of IL-33, which promotes cytokine (IL-5, IL-13) production by type 2 innate lymphoid cells (ILC2s). MicroRNA (miR)-155 has recently been described to regulate adaptive responses in allergic inflammation. However, the role of miR-155 in the regulation of ILC2s remains unexplored.

Objective: We sought to elucidate the contribution of miR-155 in ILC2 expansion using experimental murine models of allergic airway inflammation.

Methods: To determine the role of miR-155 in the regulation of ILC2s in allergic airway inflammation, miR-155 deficient (miR-155^-/-) and wild-type (WT) mice were subjected to acute or chronic allergen-induced inflammation or treated with recombinant IL-33.

Results: miR-155 was 10-fold upregulated in WT-derived ILC2s in response to IL-33. Furthermore, miR-155^-/- mice demonstrated impaired lung IL-33 levels in response to allergen challenge and the number of ILC2s was significantly reduced in allergen-challenged miR-155^-/- mice compared with WT mice. Exogenous IL-33 treatment revealed that miR-155 is needed for IL-33-induced ILC2 expansion and eosinophilic airway inflammation. Indeed, ILC2s from IL-33-challenged miR-155^-/- lungs exhibited impaired proliferation, GATA-3 expression, and IL-13 production as compared with IL-33-challenged WT ILC2s.

Conclusions: Our findings for the first time demonstrate that ILC2s and IL-33 signaling are regulated by miR-155 in allergic airway inflammation.

Keywords: IL-13; IL-33; ILC2; allergy; asthma; eosinophils; miR-155.