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- W4313368829 abstract "Abstract BACKGROUND Exposure to innocuous inhaled foreign antigens such as dust mite and pollen triggers aberrant immune responses in the respiratory tract of individuals genetically predisposed to asthma. Immune tolerance restricts such overreaction and plays a key role in preventing unwanted inflammatory responses. Yet the mechanisms underlying this protection are still largely unclear. Our studies of immune tolerance in regulation of experimental asthma and those of others in the context of cancer demonstrated PPARγ-facilitated fatty acid oxidation (FAO) resulting in mitochondrial H2O2 production in dendritic cells (DCs) in promotion of immune tolerance. However, neither study addressed whether mitochondrial H2O2 is essential for suppression of inflammation in response to antigens. OBJECTIVE In this study, we sought to establish a mouse model of airway tolerance to inhaled house dust mite (HDM) allergen in newborn mice and study the role of mitochondrial H2O2 in tolerance establishment. METHODS AND RESULTS Repeated exposure of wild type (WT) mice to a low dose of the common allergen HDM in early life suppressed airway inflammation and airway hyperreactivity when the mice were challenged by a high dose of the allergen in adulthood. This protective effect was abolished in MCAT transgenic mice, which overexpress the catalase gene in their mitochondria. The inflammatory phenotype in the MCAT mice was associated with a high TH2 response facilitated by lung dendritic cells (DCs). CONCLUSIONS Our study illustrates a crucial role of mitochondrial H2O2 in the establishment of airway tolerance in early life, which suppresses DC-mediated TH2 response." @default.
- W4313368829 created "2023-01-06" @default.
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- W4313368829 date "2020-05-01" @default.
- W4313368829 modified "2023-09-30" @default.
- W4313368829 title "Establishment of airway tolerance in early life to inhaled house dust mite involves mitochondrial H2O2" @default.
- W4313368829 doi "https://doi.org/10.4049/jimmunol.204.supp.147.27" @default.
- W4313368829 hasPublicationYear "2020" @default.
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