Combined application: Dr Woods and Ms Doherty

自身免疫性疾病的控制和有效治疗仍然是我们卫生系统面临的主要挑战。多发性硬化症、系统性红斑狼疮、糖尿病和恶性贫血等疾病基本上是无法治愈的严重疾病。目前的治疗方法只在提供暂时缓解方面有效，因为它不是针对潜在的疾病过程。这个项目将以这样一种方式操纵免疫系统，即阻止自身免疫中的早期疾病过程，最终目标是治愈疾病。使用小鼠恶性贫血的实验模型，其基本病理是免疫介导性胃炎，这种疾病的治疗方法是通过修饰的或未成熟的抗原提呈细胞将引起自身抗原的疾病递呈给免疫系统。在构成该项目背景的其他实验模型中，我们已经表明，这种方法通过产生专门抑制免疫系统的细胞来下调免疫反应。在自身免疫性胃炎的研究中，我们将从皮肤、血液、脾和胸腺获得修饰的抗原提呈细胞，并利用这些细胞来确定递呈自身抗原分子的最佳条件，以达到最终目的，即抗原特异性抑制自身免疫性胃炎。我们的假设是，未成熟的抗原提呈细胞不能提呈抗原来诱导有效的免疫反应，而是诱导导致抗原特异性抑制的反应。我们打算使用这种抗原特异性抑制来预防自身免疫性胃炎的建立以及对既定疾病的治疗。这是治疗自身免疫性胃炎的一种独特且有潜在价值的策略，并提供了将这种方法应用于其他自身免疫性疾病的可能性。

Control and effective treatment of autoimmune diseases remain major challenges to our health system. Diseases such as multiple sclerosis, systemic lupus erythematosus, diabetes and pernicious anaemia are serious conditions that are essentially incurable. Current treatment is only effective in providing temporary relief as it is not directed against the underlying disease process. This project will manipulate the immune system in such a way that early disease processes in autoimmunity will be blocked with the ultimate goal to cure the disease. Using an experimental model of pernicious anaemia in mice, where the basic pathology is immune-mediated gastritis, the disease will be treated by presenting the disease causing autoantigen via modified, or immature, antigen presenting cells to the immune system. In other experimental models which form the background to this project we have shown that this approach leads to down-regulation of the immune response by generating cells which specifically suppress the immune system. In our studies of autoimmune gastritis we will obtain modified antigen presenting cells from the skin, the blood, the spleen and thymus and use these cells to define optimal conditions for presenting the auto-antigen molecules to achieve the ultimate goal, which is antigen specific suppression of autoimmune gastritis. Our hypothesis is that immature antigen presenting cells are unable to present antigen to induce an effective immune response, but instead induce a response that results in antigen specific suppression. We intend to use this antigen specific suppression to prevent the establishment of autoimmune gastritis as well as treatment of established disease. This is a unique and potentially valuable strategy to treat autoimmune gastritis and offers the potential to apply this approach to other autoimmune conditions