The role of phagocytic NADPH oxidase in the regulation of innate lymphoid cells in Dermatophagoides pteronyssinus-induced lung inflammation

Abstract

Asthma is a chronic inflammatory disease of the airway induced by exogenous allergens The most important allergen in Taiwan is house dust mites (HDMs) which affects people in all ages including children The characteristics of asthma are airway inflammation and airway hyperresponsiveness (AHR) In asthma immune cells particular eosinophils and T cells infiltrate into airways and increase the expression of type 2 inflammatory cytokines Previous studies indicated that phagocytic NADPH oxidase (NOX2) is an essential regulator in allergen-induced airway inflammation characterized by a severe lung inflammation with Th17 immune response and decreased lung inflammation in the absence of NOX2 Changes in the redox balance by defective NOX2 may affect lung inflammation in term of early innate immune cell activation/recruitment and the subsequent specific immune responses Innate lymphoid cell (ILCs) have been known to play an important role in the development of lymphoid tissues and in the initiation of inflammation in response to infection or tissue damage Therefore we used allergens including Dermatophagoides pteronyssinus (Der p) and ovalbumin (OVA) to stimulate NOX2-deficient mice to address the hypothesis that Der p or OVA-induced allergic lung inflammation are affected in NOX2 deficient mice due to different ILC-mediated immune responses In this study allergen-induced asthma models had been established by intranasal administration of Der p or OVA in WT and Ncf1-/- mice at 8-9 weeks of age First we investigated the role of NOX2 in airway inflammation by using WT and Ncf1-/- mice with Der p or OVA exposure We found that Der p induced AHR and increased IgE production inflammatory cells and mucus infiltration around the bronchiole in WT and Ncf1-/- mice OVA exposure induced AHR and increased IgE production inflammatory cells and mucosa infiltration around the bronchiole in WT mice but not in Ncf1-/- mice Second we determined the effects of Der p or OVA on induction of Th2 cytokines (including IL?4 5 13) and Th17 cytokines (IL-17) production in the lung of WT and Ncf1-/- mice Moreover we analyzed the immune cell of the lung tissue by flow cytometry to identify lung inflammation of WT and Ncf1-/- mice We found that after Der p exposure eosinophils and type 2 cytokines are induced in WT mice and then neutrophils and IL-17 are increased in Ncf1-/- mice with Der p exposure After OVA exposure eosinophils were induced in WT mice but not in Ncf1-/- mice Finally we studied the cell surface markers expression to characterize the ILC subsets in the lung of Der p or OVA- induced mice in both WT and Ncf1-/- mice We found that ILC2s number increased in lung tissue after Der p exposure in WT and Ncf1-/- mice ILC2s number also increased in lung tissue after OVA exposure in WT but not in Ncf1-/- mice Our data indicate that changes in ILCs activity may have a role in phagocytic NADPH oxidase-mediated immune regulation in Der p and OVA-induced airway inflammation

Date of Award	2019
Original language	English
Supervisor	Chi-Chang Shieh (Supervisor)