Background The pathogenesis of allergic asthma is classically understood to involve allergens crosslinking Immunoglobulin E (IgE) bound to mast cells and basophils, leading to the release of inflammatory mediators. However, omalizumab, an anti-IgE antibody, reduces exacerbation rates in only about 40% of adult patients with severe asthma. These findings highlight the need for further research to fully address the role of IgE in allergic diseases like asthma. This study aims to explore which allergen induces Th2-associated airway inflammation through an IgE-dependent mechanism.

Methods We used IgE deficient mice (IgE KO) to generate asthma mouse models induced by two highly clinically relevant allergens house dust mite extract (HDM), cockroach extract (CRE) and one classic allergen ovalbumin (OVA). Hematoxylin and Eosin (HE) staining and Alcian Blue-Periodic Acid-Schiff (AB-PAS) staining was performed on lung tissue to evaluate inflammatory responses and mucus production, respectively. The count of inflammatory cells in Bronchial Alveolar Lavage Fluids (BALF) was determined using flow cytometry. Passive Cutaneous Anaphylaxis (PCA) was conducted to quantify IgE involvement in the anaphylactic reaction, and Toluidine Blue (TB) staining of dorsal skin tissue was used to visualize mast cell recruitment.

Results All mice treated with allergens exhibited significant signs of airway inflammation, as evidenced by the recruitment of inflammatory cells to the lung parenchyma and goblet cell hyperplasia. However, IgE KO mice treated with different allergens demonstrated significantly variable degrees of inflammation compared to the WT control. Of these, HDM-treated IgE KO mice showed an attenuated inflammatory profile with reduced inflammatory cells, particularly eosinophils. These mice had lower serum levels of HDM-specific IgE1 (sIgE1) and IgG1 (sIgG1) and reduced levels of Th2 cytokines IL-4 and IL-5 in BALF. While CRE-treated IgE KO mice also displayed a reduced inflammation compared to WT mice, the only statistically significant difference was found for eosinophils. No significant differences were observed between OVA-treated IgE KO and WT mice. These findings were further supported by our well-established PCA models. Both HDM and CRE-induced PCA model showed significantly less Evan’s blue dye leakage and mast cell recruitment in the ears of IgE KO mice compared to WT mice. No differences were observed for OVA-induced PCA and mast cell recruitment.

Conclusion The results highlight the variability in IgE pathway dependence among different allergens, emphasizing the need for further research is to delineate the mechanisms and develop more effective therapeutic strategies for allergic diseases.