Farm dust and endotoxin protect against allergy through A20 induction in lung epithelial cells

作者：Martijn J. Schuijs, Monique A. M. Willart, Karl Vergote, Delphine Gras, Kim Deswarte, Markus Johannes Ege, Filipe Branco Madeira, Rudi Beyaert, Geert Loo, Franz Bracher, Erika von Mutius, Pascal Chanez, Bart N. Lambrecht, Hamida Hammad · 发表于：Science · 年份：2015 · DOI：10.1126/science.aac6623 · 被引用次数：586 · 研究领域：IL-33, ST2, and ILC Pathways、Asthma and respiratory diseases、Immune Response and Inflammation

Growing up on a dairy farm protects children from allergy, hay fever, and asthma. A mechanism 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 polymorphism 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.