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2621611 
Journal Article 
Abstract 
Farm dust downregulates Th2 driven allergic airway inflammation in mice: a role for epithelial TLR2 and TLR4 
Blacquiere, MJ; Postma, DS; Timens, W; Geerlings, M; Spaans, F; Holst, O; Bufe, A; Hylkema, MN 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A4046 
English 
WOS:000208771003390 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
Rationale: Exposure to farm dust, collected from cowsheds in rural environments in the Alps, decreased allergic sensitisation, eosinophilic airway inflammation and airway responsiveness in a mouse model of ovalbumin induced allergic airway inflammation. The mechanisms inducing protection from Th2 driven allergic airway inflammation were not investigated in detail. We first studied whether farm dust collected at different farms also protects from allergic airway inflammation in a different mouse model of allergic airway inflammation, i.e the house dust mite (HDM) model. Furthermore, since literature shows that Toll-like receptor (TLR)4 on structural airway cells was necessary for the HDM-induced allergic airway response, we studied the role of TLR expression in the effects of farm dust in HDM-exposed mice.

Methods: Dust from cowsheds at five different farms in North Germany was collected, extracted and pooled. Mice were intranasally exposed 4 times/week for 5 weeks to phosphate buffered saline (PBS) or farm dust (1 mg/ml, 50 µl/day), followed by PBS or HDM (2.5 mg/ml, 10 µl/day). Goblet cell hyperplasia and inflammatory cells and mediators were measured in lung tissue and serum and TLR2 and TLR4 expression on epithelial cells was assessed.

Results: Farm dust+HDM exposed mice had lower levels of eosinophilic inflammation (Figure 1), HDM-specific IgE in serum and T 2H cytokines in the lung than HDM expose mice. Furthermore, TLR2 and TLR4 (Figure 2) expression in epithelium as well as the epithelium derived cytokine thymic stromal lymphopoietin (TSLP) were lower in farm dust exposed mice than in HDM exposed mice. Additionally, we observed less spindle shaped CD68+ cells beneath the epithelial basement membrane in farm dust exposed mice.

Conclusion: Lower expression of TLR2 and TLR4 in epithelium of farm dust exposed mice may lead to decreased production of TSLP by epithelial cells. Lack of TSLP could have prevented recruitment of antigen presenting cells (which may be evidenced by the spindle shaped CD68+ cells we observed) beneath the epithelial basement membrane, thereby decreasing allergic sensitisation and airway inflammation in farm dust exposed mice. 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010