The absence of VPAC2 leads to aberrant antibody production in Aspergillus fumigatus sensitized and challenged mice

Vasoactive intestinal peptide (VIP) facilitates a “pro-allergy” phenotype when signaling through its G protein-coupled receptor, VPAC2. We have shown that VPAC2 knock-out (KO) mice developed an allergic phenotype marked by eosinophilia and elevated serum IgE. Therefore, we hypothesized that the humoral response to allergen challenge in these mice was TH2 dominant similar to wild-type (WT) C57BL/6 mice. Antibody responses in WT and KO mice were measured after Aspergillus fumigatus conidia inhalation. In contrast to previous reports, basal levels of serum IgG2a and IgA were significantly higher in naïve VPAC2 KO animals. Antibody availability in the serum as well as the bronchoalveolar lavage fluid after fungal challenge was dominated by the pro-inflammatory isotype IgG2a and the mucosal isotype, IgA. IgA localizing cells dominated in the peribronchovascular areas of allergic KO mice while IgE immune complexes were found in WT allergic lungs. This research shows for the first time that VPAC2 has a significant effect on antibody regulation, in the context of allergy.

Research highlights▶ Naïve mice lacking the inducible VPAC2 receptor produce more IgG2a and IgA. ▶ VPAC2 null mice sustain elevated IgG2a and IgA in sera after allergen challenge. ▶ Mucosal antibodies are dominated by IgG2a and IgA in allergic VPAC2 null mice. ▶ First evidence that VPAC2 absence leads to a dysregulation in antibody production.