IL-33 elicits IL-5 dependent eosinophilia in vivo

Abstract

Abstract Introduction Interleukin (IL)-33 plays important roles in the immunopathogenesis of allergy and asthma. It acts by promoting IL-5 and IL-13 secretion from IL-33 responsive type 2 innate lymphoid cells (ILC2s) or directly activates eosinophils and mast cells. IL-5 is crucial in eosinophilic inflammation by controlling differentiation and survival of eosinophils in the bone marrow as well as release and recruitment of eosinophils to the airways. While ILC2s have emerged as important producers of IL-5 in airways, the cellular source of IL-5 in the bone marrow is less explored. In this study we tested the hypothesis that IL-33 induced airway eosinophilia is an IL-5 dependent process in which ILC2s produce IL-5 locally in the bone marrow. Methods IL-5 production by bone marrow ILC2s was analyzed by intracellular flow cytometry in a murine model of IL-33 induced airway eosinophilia. Results Intranasal IL-33 administration resulted in eosinophil infiltration in airways and increased eosinophils in bone marrow. It was accompanied by a dramatic induction of eotaxin-2 in airways, indicating eosinophil recruitment to the tissue. IL-5+ ILC2s as well as expression of the IL-33 receptor on ILC2s increased in the bone marrow in response to IL-33 administration. Importantly, airway and bone marrow eosinophils were greatly reduced in mice pre-treated with anti-IL-5 antibodies followed by intranasal IL-33. Conclusion Our results demonstrate that IL-33 elicits IL-5 dependent eosinophilia in vivo, where ILC2s represent a local source of IL-5 in the bone marrow.