How farming protects against allergies People who grow up on dairy farms only rarely develop asthma or allergies. This is probably because as children, they breathe air containing bacterial components, which reduce the overall reactivity of the immune system. Schuijs et al. chronically exposed mice to bacterial endotoxin before they received an allergic stimulus. The protocol indeed protected them from developing an allergic response. Protection relied on a particular enzyme: A20. In humans, a variant of A20 correlates with increased susceptibility to asthma and allergy in children growing up on farms. Science, this issue p. 1106 Chronic exposure to bacterial endotoxin protects against allergy through the enzyme A20. 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.