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Distinct "asthma" phenotypes of four mouse strains correlate with different responses to house dust mite (HDM) allergens


Baines,  J.
Guest Group Evolutionary Genomics, Max Planck Institute for Evolutionary Biology, Max Planck Society;

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Lund, J., Bartel, S., Orinska, Z., Lunding, L., Kull, S., Baines, J., et al. (2018). Distinct "asthma" phenotypes of four mouse strains correlate with different responses to house dust mite (HDM) allergens. Allergy, 73(SI), 343-343. doi:DOI: 10.1111/all.13538.

Cite as: http://hdl.handle.net/21.11116/0000-0002-6BB4-B
Background: Asthma is a heterogeneous disease comprising different phenotypes. The corresponding “endotypes” are currently insufficiently understood thus hampering the development of personalized treatments. As a first step in this direction, models for experimental asthma reflecting different asthma phenotypes and endotypes need to be developed. Thus, we aimed to develop a murine model for the investigation of different responses to single Der p allergens. Method: Female mice of four different strains were obtained from Jackson Laboratory. Experimental asthma was induced by intranasal administration of 20 μg HDM extract (D. pteronyssinus extract, Greer, USA) three times weekly/ three weeks. Asthma phenotypes were evaluated by lung function measurements, histology, gene expression, immune cell infiltration, cytokine levels in broncho‐alveolar lavage (BAL) and total and allergen specific IgE in sera. Results: Higher airway resistance, elevated levels of BAL cell and eosinophil numbers, increased levels of IgE in sera and goblet cell hyperplasia were observed in all HDM treated animals in contrast to PBS‐treated controls. Initial tests measuring single anti‐Der p‐IgE reactivities (Der p 1, Der p 2, Der p 7, Der p 20, Der p 21, Der p 23) revealed distinct sensitization patterns for the different strains. The gene expression levels of MUC5B (fold‐change to control A/J: 7.5; BALB/cJ: 3.5; C57Bl/6J: 4.1; C3H/HeJ: 8.5) and CCL11(foldchange to control A/J: 72.7; BALB/cJ: 8.1; C57Bl/6J: 21.1; C3H/HeJ: 21.1) showed differences among the four strains. Combining all these results allowed us to characterize distinct “asthma” phenotypes, ranging from low eosinophilic, Th2 low (“low susceptible”) over an “intermediate susceptible” Th17 high to a mainly eosinophilic, Th2‐dominated phenotype with pronounced changes in lung histology (“high susceptible”). Conclusion: Applying the same HDM treatment in four different mouse strains resulted in distinct asthma phenotypes and showed for the very first time different sensitization patterns. In future studies, we will investigate the mechanisms underlying these different responses to different single Der p allergens and if possible investigate these in human asthma patients as well.