Inhibition of CD23-Mediated IgE Transcytosis Suppresses the Initiation and Development of Allergic Airway Inflammation

The epithelial lining of the airway tract and IgE are considered essential controllers of inflammatory responses. CD23 is capable of transporting IgE or IgE-allergen complexes across the human airway epithelial cells (AEC) in vitro. However, it remains unknown whether the CD23-dependent IgE transfer pathway in AECs initiates and facilitates allergic inflammation in vivo, and whether inhibition of this pathway attenuates allergic inflammation. Here, we show that in wild-type (WT) mice, epithelial CD23 transcytosed both IgE and OVA-IgE complexes across the airway epithelial barrier, while neither type of transcytosis was observed in CD23 knockout (KO) mice. In chimeric mice, OVA sensitization and aerosol challenge of WT/WT (bone-marrow transfer from the WT to WT) or CD23KO/WT (CD23KO to WT) chimeric mice, which express CD23 on radioresistant airway structural cells (mainly epithelial cells) resulted in airway eosinophilia, including collagen deposition and a significant increase in goblet cells, and increased airway hyperreactivity. In contrast, the absence of CD23 expression on airway structural or epithelial cells, but not on hematopoietic cells, in WT/CD23KO (the WT to CD23KO) chimeric mice significantly reduced OVA-driven allergic airway inflammation. In addition, inhalation of the CD23-blocking B3B4 antibody in sensitized WT mice before or during challenge suppressed the salient features of asthma, including bronchial hyperreactivity. These results identify a previously unproven mechanism in which epithelial CD23 plays a central role in the development of allergic inflammation. Further, our study suggests that inhibition of CD23 in the airway is a potential therapeutic approach with which to inhibit the development of asthma.