Farm dust and endotoxin protect against allergy through A20 induction in lung epithelial cells
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
Abstract
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.
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Published In
Science
Volume 349 | Issue 6252
4 September 2015
4 September 2015
Copyright
Copyright © 2015, American Association for the Advancement of Science.
Submission history
Received: 27 May 2015
Accepted: 27 July 2015
Published in print: 4 September 2015
Acknowledgments
The data reported in this manuscript are tabulated in the main paper and in the supplementary materials. M.J.E. and E.v.M have filed patent applications (EP000002361632B1, EP000001964570B1, and US020080305089A1) that relate to identifying microorganisms and derived substances in farm dust that induce protection from several inflammatory diseases. This research was supported by European Union FP7 grant “MedALL” (Mechanisms in Development of Allergy) and by a European Union Innovative Medicines Initiative grant “EUBIOPRED.” H.H. and B.N.L. are recipients of several Flanders Organization for Scientific Research (FWO) program grants. B.N.L. is a recipient of a European Research Council Consolidator grant and a Ghent University Multidisciplinary Research Platform grant (Group-ID). D.G. and P.C. are supported by grants from ARARD, Fonds de Recherche en Santé Respiratoire, and ANR “Mucocil.” Population analyses were supported by two European Union research grants (GABRIEL: LSHB-CT-2006-018996, HERA: ERC2009-AdG_20090506_250268). E.v.M is supported by a Gottfried-Wilhelm-Leibniz award from the German Research Council. M.J.E. and E.v.M. are members of the German Center for Lung Research (DZL).
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- Martijn J. Schuijs et al.
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