The research team at the Flanders Institute for Biotechnology (VIB) headed by Bart Lambrecht and Hamida Hammad has shown that children growing up on a farm are protected against asthma. They also uncovered a mechanism by which this resistance occurs and pinpointed A20 as a crucial protein in this process. Further research based on these results was published in the high-impact journal Science and might aid in the development of an asthma vaccine.
Asthma originates as an inflammatory response to inhaled allergens such as house dust mites and pollen. It is thought that the rise in asthmas and allergies is due to a reduction in the infection pressure due to the modern western lifestyle that has been adopted over the last couple of decades. Early exposure to farm dust appears to protect children from asthma, hay fever and other allergies. The first set of experiments the researchers conducted demonstrated this effect in mice: animals exposed to farm dust did not develop asthma after sensitization and challenge with house dust mite (HDM), whereas the control group did show HDM-induced-asthma features.
A20 confers protection
The ubiquitin-editing protein A20 was shown to play an essential role in mediating the protective response to farm dust. The researchers showed in a second set of experiments that A20 is upregulated in the lung epithelial cells of mice that were exposed to farm dust. A20 blocks the production of several dendritic cell-attracting cytokines, which results in a dampening of the allergic response. While wild-type mice were resistant to HDM-induced asthma after farm dust exposure, A20 knock-out mice did not respond to farm dust and developed asthma-like features.
This also applied to humans, as patients treated for asthma and other allergies displayed a shortage of the beneficial A20 protein compared to healthy individuals. Within a group of children growing up on farms, children sensitive to asthma contained a single-nucleotide polymorphism (SNP) in the gene coding for A20, TNFAIP3. This genetic variant does not function properly, increasing the risk for developing asthma. These facts suggest an important function of A20 in the resistance against asthma and the balancing of immune cells in allergies.
A cure for asthma?
Identification of the active substance within the farm dust that triggers the upregulation of A20 is an important next step. The researchers already suspect that lipopolysaccharide (LPS), a component of the cell wall of Gram-negative bacteria that is present in large quantities in farm dust, is a good candidate. However, farm dust may also contain other active components that may also be involved. Identification of a potent protective mediator could allow for the development of new allergy therapies or perhaps even an asthma vaccine.
References
Schuijs, Martijn J., et al. “Farm dust and endotoxin protect against allergy through A20 induction in lung epithelial cells.” Science 349.6252 (2015): 1106-1110.
(Image courtesy of Maggie Smith at FreeDigitalPhotos.net)
