Inhibition of CD23-mediated IgE transcytosis suppresses the initiation and development of airway allergic inflammation (HYP4P.308)

Abstract

Abstract The human low affinity IgE receptor, CD23 (FceRII), is capable of transporting IgE or IgE-allergen complexes across the polarized human airway epithelial cell (AEC) monolayer in vitro. However, it remains completely unknown whether CD23-dependent IgE transfer pathway in AECs initiates and facilitates allergic inflammation in vivo. To prove this, we first showed that epithelial CD23 in wild-type (WT) mice transcytosed either IgE or ovalbumin (OVA)-IgE complexes across the airway epithelial barrier. Neither type of transcytosis was observed in CD23-knockout (KO) mice. The OVA sensitization and aerosol challenge of the irradiated WT/WT or CD23KO/WT chimeric mice that CD23 expressed on radioresistant airway structural cells, mainly in epithelial cells, resulted in airway eosinophilia, lung damages including collagen deposition and significantly increased goblet cells, and increased airways hyperreactivity. In contrast, the absence of CD23 expression on airway structural or epithelial cells, but not on hematopoietic cells, of the bone-marrow chimeric mice (WT/CD23KO) significantly reduced OVA-driven allergic airway inflammation. Finally inhalation of a CD23-blocking B3B4 antibody to target exposed CD23 in AECs of the sensitized WT mice before airway challenge suppressed the salient features of asthma, including bronchial hyperreactivity. Our study further suggests that the functional inhibition of CD23 on AECs is a potential therapeutic means to intervene the asthma development.