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

M.J. Schuijs, M.A. Willart, et al.

Science 2015: Vol. 349 no. 6252 pp. 1106-1110

Speaker: Chia-Ying Cheng (鄭嘉瑩)                            Time: 13:10~14:00, Dec. 09, 2015

Commentator: Dr. Jiu-Yao Wang (王志堯 醫師)        Place: Room 601

Abstract:

    Allergic asthma is characterized by eosinophilic airway inflammation, which is controlled by innate and adaptive immune responses to inhaled allergens.  On farms, there is high-level of endotoxin (lipopolysaccharide (LPS)) which may protect exposed childern from allergic asthma.  However, the mechanism encompassing the complex interactions between a protective enviroment, genetics, and the immune response to allergens had not yet been addressed.  Previous studies showed that LPS induces the ubiquitin-editing enzyme A20 expression which can inhibit Toll-like receptor-induced NF-kB activation.  To investegate whether A20 play a role in endotoixn-induced protection against house dust mite (HDM)-induced asthma, the authors preexposed low-dose (100 ng) LPS to wild type mice and mice with lung specific A20 gene (Tnfaip3) knockout before HDM sensitization and challenge.  First, they found that chronic LPS preexposure protected mice from asthma development.  Second, LPS pre-exposure reduced epithelial cell chemokines that recruit dendritic cells (DCs), thus suppressed type 2 immunity to HDMs.  Third, LPS pretreatment was no longer protective against the HDM-induced allergen asthma in mice without A20 expression in lung epithelial cells.  Finally, they found that A20 expression was lower in asthma patients.  Therefore, A20 plays an important role in endotoixn-induced protection against allergic asthma in both mouse and humans.  In conclusion, farm dust and endotoxin protect against allergy asthma through A20 induction in lung epithelial cells.  This research provides a novel mechanism in the interaction between protective environment and immune response to allergens.

Reference:

1.      J. Wang, Y. Ouyang et al., Ubiquitin-Editing Enzyme A20 Promotes Tolerance to Lipopolysaccharide in Enterocytes J Immunol 183, 1384-1392 (2009)