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Title: Inhibition of CD23-mediated IgE transcytosis suppresses the initiation and development of airway allergic inflammation

item PALANIYANDI, SENTHILKUMAR - University Of Maryland
item LIU, XIAOYANG - University Of Maryland
item PERIYASAMY, SIVAKUMAR - Albany Medical College
item MA, AIYING - University Of Maryland
item Jenkins, Mark
item Tuo, Wenbin
item SONG, WENXIA - University Of Maryland
item KEEGAN, ACHSAH - University Of Maryland
item CONRAD, DANIEL - Virginia Commonwealth University
item ZHU, XIAOPING - University Of Maryland

Submitted to: Mucosal Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/1/2015
Publication Date: 3/18/2015
Citation: Palaniyandi, S., Liu, X., Periyasamy, S., Ma, A., Jenkins, M.C., Tuo, W., Song, W., Keegan, A.D., Conrad, D.H., Zhu, X. 2015. Inhibition of CD23-mediated IgE transcytosis suppresses the initiation and development of airway allergic inflammation. Mucosal Immunology. DOI:10.1038/mi.2015.16.

Interpretive Summary: Inflammatory responses to airborne allergens are controlled by epithelial cells lining the lung and airway. Better understanding the receptors that mediate transport of allergens might provide new ways to ameliorate asthma and allergic responses to airborne irritants, including lungworms and other respiratory pathogens of livestock. Here we investigated, in mice, how a particular cell surface receptor (CD23) plays a role in transporting allergens, bound by immunoglobulin E (IgE), across the lining of the airway. Mice lacking this receptor in epithelia lining the airway did not mount inflammatory responses when exposed to allergens, but did when supplemented with bone marrow donated from normal mice. Having such receptors elsewhere in the body did not lead to inflammatory responses, underscoring the requirement for this receptor on epithelial cells lining the airway. Inflammation could be suppressed by administering antibodies to this receptor. Taken together, the present study identified a mechanism where epithelial CD23 mediates respiratory inflammation. Blocking CD23 may be a therapeutic method to prevent or ameliorate asthma. These results may interest immunologists, veterinarians, and the pharmaceutical industry, and others interested in infectious and non-infectious induced respiratory disease.

Technical Abstract: The epithelium lining the airway tract and allergen-specific IgE are considered essential controllers of inflammatory responses to allergens. The human IgE receptor, CD23 (Fc'RII), 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 and whether the inhibition of such a pathway can attenuate the allergic inflammation. 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 bone-marrow chimeric mice (WT/WT) 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 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 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 in vivo. Our study further suggests that the functional inhibition of CD23 on AECs is a potential therapeutic means to intervene the asthma development.