Effects of environmental exposures on asthma phenotypes in the mouse. Contributing and protecting mechanisms

Promotie: mw. M.J. Blacquière, 16.15 uur, Academiegebouw, Broerstraat 5, Groningen

Proefschrift: Effects of environmental exposures on asthma phenotypes in the mouse. Contributing and protecting mechanisms

Promotor(s): prof.dr. W. Timens, prof.dr. D.S. Postma

Faculteit: Medische Wetenschappen

Contact: via de persvoorlichters van het UMCG, tel. 050-361 2200, e-mail: voorlichting bvl.umcg.nl

Effects of environmental exposures on asthma phenotypes in the mouse. Contributing and protecting mechanisms

Asthma is a common disease in which an exaggerated immune response to inhaled allergens, combined with remodeling (scarring) of the lung tissue induces severe shortness of breath. This thesis investigated the mechanisms via which environmental factors and sex can affect the development of asthma.

Children of women who smoked during pregnancy more often develop asthma than children of mothers that did not smoke during pregnancy. The mechanisms behind this phenomenon were not known yet. This thesis shows that in an experimental mouse model smoking during pregnancy induces airway remodeling in adult offspring, but that the immune response of the offspring is not affected. Additionally, smoking during pregnancy decreases gene expression of several genes in the Wnt signaling pathway -involved in lung development- in lungs of newborn offspring. Disruption of this gene expression may lead to an increased risk for development of asthma as well as other lung diseases.

Furthermore, growing up on a farm protects from development of asthma (hygiene hypothesis) via unknown mechanisms. In our mouse model, exposure to farm dust decreased the allergic immune response, possibly via decreased expression of TRL2 and TLR4 receptors in the airways. Despite the decreased allergic response, farm dust increased the non-allergic immune response, with a possible role for the Th17 cell.

In addition, we investigated why females have asthma more often and have a more severe type of asthma than males. Female mice show a more severe immune response to inhaled allergens than males, but airway remodeling was similar for both sexes.