探討介白質10基因在治療氣喘動物模式及誘發調節性 T 細胞之能力

Abstract

Allergic asthma strongly correlates with airway inflammation caused by the unregulated production of cytokines secreted by allergen-specific type-2 T helper (Th2) cells. The inappropriate Th2 response causes airway eosinophilic inflammation, mucus hypersecretion and airway hyperreactivity (AHR) result in the symptoms of asthma. The logical resolution of inflammation in the lung occurs through the inhibition of exaggerated Th2-mediated responses by immuno-regulatory cytokines. Both Th1-relatived cytokines, such as IL-12 , and immunosuppressive cytokines, including TGF-β and IL-10, are the candidate cytokines for the treatment of allergic diseases as they downregulate Th2 responses. In current study, we had compared the effect of several cytokines (IL-12, IL-10, TGF-β and IL-4) simultaneously on disease development in a murine model of asthma. Our data demonstrated that anti- inflammatory cytokines, particularly IL-10, have the therapeutic potential for the alleviation of airway inflammation in the asthma model in a dose-dependent manner. Furthermore, in order to achieve high local concentration of IL-10, we used IL-10-expressing adenovirus (Ad-IL-10) to elucidate the therapeutic effect of prolonged homologous IL-10 administration on airway inflammation. As our respect, localized expression of IL-10 may provide a more direct therapeutic approach for diseases of exaggerated proinflammation. However, a more attracting strategy is to enhance immune regulation, which can suppress or modulate Th2 response and cure allergic disease finally. Dendritic cells (DCs) play a crucial role in directing T helper cells differentiation and could be a good candidate of this therapeutic approach. Thus, we had examined whether Ad-IL-10 infected DCs (DC-IL-10) have the potential to induce the differentiation of Tr1-like cells by in vitro repetitive stimulation of na?ve DO11.10 CD4+ T cells with DC-IL-10 and suggest their therapeutic use. Taken together, these results suggested that application of immune-suppressive cytokine, such as IL-10, not only can suppress airway inflammation locally, but also has potential to modulate immune response by genetically modified DCs.