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¡¡¡¡Farm dust and endotoxin protect against allergy through A20 induction in lung epithelial cells
¡¡¡¡Martijn J. Schuijs1,2,*, Monique A. Willart1,2,*, Karl Vergote1,2, Delphine Gras3, Kim Deswarte1,2, Markus J. Ege4, Filipe Branco Madeira1,2, Rudi Beyaert5,6, Geert van Loo5,6, Franz Bracher7, Erika von Mutius4, Pascal Chanez3, Bart N. Lambrecht1,2,8, , , Hamida Hammad1,2, ,
¡¡¡¡Growing up on a dairy farm protects children from allergy, hay fever, and asthma. A mechani linking exposure to this endotoxin (bacterial lipopolysaccharide)–rich environment with protection has remained elusive. Here we show that chronic exposure to low-dose endotoxin or farm dust protects mice from developing house dust mite (HDM)–induced asthma. Endotoxin reduced epithelial cell cytokines that activate dendritic cells (DCs), thus suppressing type 2 immunity to HDMs. Loss of the ubiquitin-modifying enzyme A20 in lung epithelium abolished the protective effect. A single-nucleotide polymorphi in the gene encoding A20 was associated with allergy and asthma risk in children growing up on farms. Thus, the farming environment protects from allergy by modifying the communication between barrier epithelial cells and DCs through A20 induction.