Farm dust and endotoxin protect against allergy through A20 induction in lung epithelial cells.
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.
Laboratory of Immunoregulation, VIB Inflammation Research Center, Ghent, Belgium. Department of Internal Medicine, Ghent University, Ghent, Belgium.
Martijn J
MJ
Schuijs
Laboratory of Immunoregulation, VIB Inflammation Research Center, Ghent, Belgium. Department of Internal Medicine, Ghent University, Ghent, Belgium.
Monique A
MA
Willart
Laboratory of Immunoregulation, VIB Inflammation Research Center, Ghent, Belgium. Department of Internal Medicine, Ghent University, Ghent, Belgium.
Karl
K
Vergote
Department of Respiratory Medicine, Assistance Publique Hopitaux de Marseille, UMR INSERM U1067 CNRS 7333, Aix Marseille University, Marseille, France.
Delphine
D
Gras
Laboratory of Immunoregulation, VIB Inflammation Research Center, Ghent, Belgium. Department of Internal Medicine, Ghent University, Ghent, Belgium.
Kim
K
Deswarte
Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität, Munich, Germany.
Markus J
MJ
Ege
Laboratory of Immunoregulation, VIB Inflammation Research Center, Ghent, Belgium. Department of Internal Medicine, Ghent University, Ghent, Belgium.
Filipe Branco
FB
Madeira
Unit of Molecular Signal Transduction, VIB Inflammation Research Center, Ghent, Belgium. Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
Rudi
R
Beyaert
Unit of Molecular Signal Transduction, VIB Inflammation Research Center, Ghent, Belgium. Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
Geert
G
van Loo
Center for Drug Research, Department of Pharmacy, Ludwig Maximilians University, Butenandtstrasse 5-13, D-81377 Munich, Germany.
Franz
F
Bracher
Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität, Munich, Germany.
Erika
E
von Mutius
Department of Respiratory Medicine, Assistance Publique Hopitaux de Marseille, UMR INSERM U1067 CNRS 7333, Aix Marseille University, Marseille, France.
Pascal
P
Chanez
Laboratory of Immunoregulation, VIB Inflammation Research Center, Ghent, Belgium. Department of Internal Medicine, Ghent University, Ghent, Belgium. Department of Pulmonary Medicine, Erasmus Medical Center, Rotterdam, Netherlands. hamida.hammad@ugent.be bart.lambrecht@ugent.be.
Bart N
BN
Lambrecht
Laboratory of Immunoregulation, VIB Inflammation Research Center, Ghent, Belgium. Department of Internal Medicine, Ghent University, Ghent, Belgium. hamida.hammad@ugent.be bart.lambrecht@ugent.be.
Hamida
H
Hammad
D000818:Animals; D001249:Asthma / Q000276:immunology / Q000517:prevention & control; D002478:Cells, Cultured; D002648:Child; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D003612:Dairying; D003713:Dendritic Cells / Q000276:immunology; D004391:Dust / Q000276:immunology*; D005260:Female; D006801:Humans; D061148:Hygiene Hypothesis; D006967:Hypersensitivity / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control*; D019570:Inhalation Exposure; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000276:immunology*; D008168:Lung / Q000201:enzymology* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000096:biosynthesis*; D039981:Pyroglyphidae / Q000276:immunology*; D020545:Respiratory Mucosa / Q000201:enzymology* / Q000276:immunology; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
D004268:DNA-Binding Proteins; D004391:Dust; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D009687:Nuclear Proteins; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3