| Summary: | 碩士 === 臺北醫學大學 === 醫學科學研究所 === 96 === Dendritic cells (DCs), a professional antigen-presenting cell type, are able to shape the immune response bridging the innate immunity and adaptive response. Now, allergic problem is more and more serious. Allergic diseases, such as asthma and food allergy, are characterized by elevated IgE/Th2 response and failed tolerance. C-type lectin receptors (CLRs) on DCs play a crucial role in determining either immunity or tolerance via recognition of specific carbohydrate moieties, but their role in the development and regulation of allergic responses has remained elusive. It was hypothesized that allergens containing complex glycan structures are natural ligands for CLRs on DCs, affecting subsequent DC’s and adaptive immune responses. I further hypothesized that differential DC responses to allergens can be found in a cohort of study subjects. Using monocyte-derived DCs (MDDCs) as a model, it was found that the carbohydrate structures on two model allergens, Der p 2 and BG60, are very important for the interaction with a member of the CLRs, DC-SIGN, and this interaction leads to the activation of Raf-1 kinase and p65 of NF-?羠 subunit to trigger the TNF-?? gene expression in MDDCs. Also, I found that MDDCs from certain individuals were not able to respond to allergen stimulation, which was associated with the lack of Raf-1 activation. Interestingly, MDDCs from all study individuals showed the induction of osteopontin, an anti-inflammatory and pro-inflammatory cytokine, following allergen stimulation. These results suggest that the glycan structures of allergens may serve as the “molecular pattern” in functional interaction with CLRs, and that the differential responses of MDDCs from different subjects may be a critical contributing factor to the expression of allergic responses.
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