title: Inhibition of CD23-mediated IgE transcytosis suppresses the initiation and development of allergic airway inflammation.
abstract: The epithelial lining of the airway tract and allergen-specific IgE are considered essential controllers of inflammatory responses to allergens. The human low affinity IgE receptor, CD23 (FcɛRII), is capable of transporting IgE or IgE-allergen complexes across the polarized human airway epithelial cell (AEC) monolayer 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. To this end, we show that in wild-type (WT) mice, epithelial CD23 transcytosed both IgE and ovalbumin (OVA)-IgE complexes across the airway epithelial barrier, whereas 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 airway challenge suppressed the salient features of asthma, including bronchial hyperreactivity. Taken together, 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 functional inhibition of CD23 in the airway is a potential therapeutic approach to inhibit the development of asthma.
authors.affiliation: Division of Immunology, Virginia-Maryland College of Veterinary Medicine, University of Maryland, College Park, MD, USA.|Maryland Pathogen Research Institute, University of Maryland, College Park, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Palaniyandi
authors.affiliation: Division of Immunology, Virginia-Maryland College of Veterinary Medicine, University of Maryland, College Park, MD, USA.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Periasamy
authors.affiliation: Division of Immunology, Virginia-Maryland College of Veterinary Medicine, University of Maryland, College Park, MD, USA.
authors.forename: A
authors.initials: A
authors.lastname: Ma
authors.affiliation: Division of Immunology, Virginia-Maryland College of Veterinary Medicine, University of Maryland, College Park, MD, USA.
authors.forename: J
authors.initials: J
authors.lastname: Tang
authors.affiliation: Animal Parasitic Diseases Laboratory, Agricultural Research Service, United States Department of Agriculture, Beltsville, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Jenkins
authors.affiliation: Animal Parasitic Diseases Laboratory, Agricultural Research Service, United States Department of Agriculture, Beltsville, MD, USA.
authors.forename: W
authors.initials: W
authors.lastname: Tuo
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA.|Maryland Pathogen Research Institute, University of Maryland, College Park, MD, USA.
authors.forename: W
authors.initials: W
authors.lastname: Song
authors.affiliation: Center for Vascular and Inflammatory Diseases and Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Keegan
authors.affiliation: Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Conrad
authors.affiliation: Division of Immunology, Virginia-Maryland College of Veterinary Medicine, University of Maryland, College Park, MD, USA.|Maryland Pathogen Research Institute, University of Maryland, College Park, MD, USA.
authors.forename: X
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism*; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D017455:Receptors, IgE / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D057900:Transcytosis / Q000276:immunology*
chemical_list: D017455:Receptors, IgE; D007073:Immunoglobulin E