IgE and FcϵRIα do not promote allergic airway disease in mice inoculated intratracheally with house dust mite extract (HYP7P.316)

The role of IgE in asthma pathogenesis is controversial. Early studies showed IgE contributed to allergic airway disease (AAD) when mice were sensitized passively by anti-ovalbumin (OVA) IgE or sensitized actively by OVA without adjuvant. Other groups found that IgE did not promote AAD that was provoked by fungal extracts or by OVA with adjuvant. We have used IgE-deficient mice and FcϵRIα-deficient mice and their respective FVBN and BALB/c wild-type controls to study the IgE- and FcϵRIα-dependence of AAD induced by a clinically relevant allergen and route of administration. Mice were inoculated intratracheally with house dust mite extract without adjuvant every 2 days for 7 doses. We measured airway hyperresponsiveness by both unrestrained plethysmography (Buxco) and forced oscillation (flexiVent), analyzed pulmonary inflammation by differential cell count on BALF, and sectioned lungs to quantitate goblet cell metaplasia by microscopic examination. We found no difference in any of these disease parameters between wild-type mice and gene-deficient mice, regardless of whether minimal, moderate, or more severe AAD was induced. These results complement the clinical observation that anti-IgE therapy fails to improve the underlying lung function of humans with long standing asthma, although this treatment does reduce acute exacerbations. We are currently studying the acute changes in lung function that occur upon inhalation of allergen in AAD and their dependence on the IgE axis.