2012-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/647440摘要：過敏性氣喘是一種呼吸道發炎反應，其特徵為嗜酸性白血球及Th2細胞增加。Th2細胞在過敏性氣喘中非常重要，其分泌IL-4, IL-5及IL-13，可促進IgE轉換，肥大細胞生成，goblet cell 增生，以及嗜酸性白血球的成熟和增生。IL-21是第一型細胞激素，由活化的T細胞分泌，IL-21 receptor表現在多種免疫細胞包括T 細胞上，IL-21對淋巴及非淋巴球均有調節作用。然而，IL-21對Th2 細胞的調控仍然未知。我們先前的研究發現，Th2媒介之異位性皮膚炎病人血液中的IL-21較正常人低，且疾病嚴重者最低。在以OVA致敏的過敏性氣喘小鼠的研究中亦發現，給予-GalCer的OVA致敏小鼠其肺沖洗液中Th2細胞激素均較低，而給予-GalCer會增加IL-21的產生。因此，我們認為IL-21會抑制Th2 過敏反應。本研究計畫將利用過敏原引起之Th2模式探討in vitro和in vivo情況下IL-21對Th2細胞分化及Th2 免疫反應之影響。子計畫如下：一、探討IL-21在給予-GalCer的OVA致敏小鼠的Th2細胞激素降低中的角色。 二、 IL-21對Th2細胞分化之影響。三、 IL-21對Th2免疫反應之影響。藉由此研究，我們將可了解IL-21是否及如何影響Th2過敏免疫反應。給與IL-21或抑制IL-21將可做為避免或治療Th2媒介疾病的策略。<br> Abstract: Allergic asthma is associated with an inflammatory process characterized by the increased presence of eosinophils and Th2 cells in the airway. Th2 cells play a major role in the development of asthma by producing cytokines such as interleukin (IL)-4, IL-5, and IL-13 to enhance IgE class switching, mast cell production, goblet cell hyperplasia, mucus hypersecretion and the maturation, activation, and accumulation of eosinophils. IL-21 is a type I cytokine that is produced by activated T cells. IL-21 receptors express on various immune cells including T cells. IL-21 exerts a variety of regulatory effects on both lymphoid and non-lymphoid cells. However, the effects of IL-21 on Th2 cells are unclear. Our previous study regarding patients with atopic dermatitis, which is a Th2 mediated allergic disease with elevated serum level of IgE, demonstrated that serum levels of IL-21 were significantly decreased in patients with atopic dermatitis compared to healthy controls. In allergic mouse study, we found significant decrease of Th2 cytokines including IL-4, IL-5 and IL-13 in OVA-immunized mice injected with -GalCer, the most studied glycolipid that activates iNKT cells, and intranasal injection of -GalCer induced various cytokines including IL-21. From these results, we propose that IL-21 would downregulate allergic Th2 immune responses.The overall goal of the current application is to investigate the effects of IL-21 on the differentiation of naïve T helper cells to Th2 cells and IL-21 on the regulation of Th2 effector immune responses in vivo and in vitro using an allergen-induced Th2 model. The specific aims are as follows: 1) Determine the role of IL-21 in the Th2 cytokine reduction of -GalCer injected OVA-immunized mice. 2) Determine the effects of IL-21 on the differentiation of Th2 cells. 3) Determine the effects of IL-21 on the regulation of Th2 effector immune responses.By this study, we will clarify whether and how IL-21 influences the differentiation of Th2 cells and the functions of Th2 effector cells. Administration of IL-21 or blocking of IL-21 may be an alternative preventive and therapeutic approach in Th2 mediated allergic diseases.過敏免疫反應-GalCerTh2IL-21allergic immune response-GalCerTh2IL-21