CD23 MEDIATED IGE TRANSCYTOSIS IN AIRWAY INFLAMMATION

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dc.contributor.advisorZhu, Xiaopingen_US
dc.contributor.authorPalaniyandi, Senthilkumaren_US
dc.contributor.departmentVeterinary Medical Scienceen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.date.accessioned2012-10-10T11:35:20Z
dc.date.available2012-10-10T11:35:20Z
dc.date.issued2012en_US
dc.description.abstractCD23 (FceRII), a C-type lectin type II membrane glycoprotein, plays an important role in IgE homeostasis and development of allergic inflammation. I showed that CD23 was constitutively expressed in the established or primary human airway epithelial cells and its expression was significantly up-regulated by IL-4 stimulation. In a transcytosis assay, human IgE or IgE derived immune complex was transported and enhanced by IL-4 stimulation across a polarized Calu-3 monolayer. A CD23 specific antibody or soluble CD23 significantly reduced the transcytosis, suggesting a specific receptor-mediated transport by CD23. Transcytosis of both IgE and the immune complex was further verified in primary human airway epithelial cell monolayers. Furthermore, the transcytosed antigen-IgE complexes were competent in inducing degranulation of the cultured human mast cells. This study implies CD23-mediated IgE transcytosis in human airway epithelial cells may play a critical role in initiating and contributing to the perpetuation of airway allergic inflammation. To verify the above results in a mouse model, CD23 expression was detected in epithelial cells lining mouse airway and enhanced by IL-4 exposure as well as in ovalbumin (OVA) sensitized mouse. I showed that CD23 transported IgE and OVA-IgE derived immune complex across airway epithelial cells in wild-type, but not CD23 knockout (KO), mice. The chimeric CD23KO mice repopulated with wild-type myeloid cells, sensitized and challenged with OVA showed significant reduction in siglec-F+ cells, eosinophils, macrophages and IL-4 in bronchoalveolar lavage fluid recovered 24 hours later compared to the wild-type mice. Our finding of CD23-mediated IgE transport in airway epithelial cells suggest a possibility of CD23 transporting an IgE Fc-fused protein for immunotherapy. CTLA-4 (Cytotoxic T-Lymphocyte Antigen 4) which competitively binds CD80 and CD86 expressed on antigen presenting cells and inhibits CD28 mediated co-stimulation of T cell activation. A CTLA4-Fc (IgE) fusion protein produced in Chinese hamster ovary cells was intranasally administrated into mouse airway for assessing its specific transport by CD23. The effect of this fusion protein on the development of allergic inflammation is being fully investigated in wild-type, CD23-KO, and chimeric mouse model.en_US
dc.identifier.urihttp://hdl.handle.net/1903/13084
dc.subject.pqcontrolledImmunologyen_US
dc.subject.pqcontrolledCellular biologyen_US
dc.subject.pquncontrolledairwayen_US
dc.subject.pquncontrolledasthmaen_US
dc.subject.pquncontrolledFc receptorsen_US
dc.subject.pquncontrolledimmune complexesen_US
dc.subject.pquncontrolledinflammationen_US
dc.subject.pquncontrolledtranscytosisen_US
dc.titleCD23 MEDIATED IGE TRANSCYTOSIS IN AIRWAY INFLAMMATIONen_US
dc.typeDissertationen_US

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