ausblenden:
Schlagwörter:
Allergy; Immunology
Zusammenfassung:
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.
