探討Notch ligand Delta4對樹突狀細胞的影響與應用於氣喘之研究

Abstract

The Notch pathway participates in cell proliferation, differentiation, and apoptosis processes that affects the development and function in various organs. Dendritic cells (DCs), as professional antigen presenting cells (APCs), induce T cell activation and promote T cells differentiation by antigen stimulation. It is known that Delta4 on APCs is associated with the stimulation of Th1-type response. However, the regulation of activation and differentiation in DCs and T cells by Delta4 remains unclear. In this study, we firstly investigated whether Delta4 played an immune-modulatory role in the activation and function of DCs in vitro. The DCs were treated with Delta4 during cells development and show low levels of MHC class Ⅱ but high level of CD80 and CD86 expression in Delta4-treated DCs. These modified DCs might be semi-mature form of DCs because they expressed low level of cytokines such as IL-12,IL-23,IL-27,IL-1β,IL-6,IL-10 and TNF-α. In addition, these Delta4-treated DCs not only inhibited the proliferation of T cells, but also reduced the production of IL-5 and IFN-γ of activated T cells. Furthermore, these modified DCs was applied to examine the preventive effects in established asthmatic animal model. In here, we showed that these modified DCs efficently moderated the characteristics of asthma, including expression of OVA-specific IgE antibody, airway hyper-responsiveness, eosinophilic airway inflammation, and cytokine production. Taken together, these results suggest that Delta4-modulated DCs are effective in suppressing asthmatic airway inflammation and are a potential therapeutic tool for asthma.