Immune tolerance to allergens in early-life decreases the risk for asthma in later life. Here we show establishment of stable airway tolerance to the allergen, house dust mite (HDM), by exposing newborn mice repeatedly to a low dose of the allergen. Lung dendritic cells (DCs) from tolerized mice induced a low Th2 response in vitro mirroring impact of tolerance in vivo. In line with our previous finding of increased mitochondrial H2O2 production from lung DCs of mice tolerized to ovalbumin, depletion of mitochondrial H2O2 in MCAT mice abrogated HDM-induced airway tolerance (Tol) with elevated Th2 effector response, airway eosinophilia, and increased airway hyperreactivity. WT-Tol mice displayed a decrease in total, cDC1 and cDC2 subsets in the lung as compared to that in naive mice. In contrast, the lungs of MCAT-Tol mice showed 3-fold higher numbers of cDCs including those of the subsets as compared to that in WT mice. Our study demonstrates an important role of mitochondrial H2O2 in constraining lung DC numbers towards establishment of early-life airway tolerance to allergens.
© 2021. The Author(s), under exclusive licence to Society for Mucosal Immunology.