Combined application: Dr Woods and Ms Doherty

控制和有效治疗自身免疫性疾病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都是严重的疾病，基本上无法治愈。目前的治疗只能有效地提供暂时的缓解，因为它不是针对潜在的疾病过程。该项目将以这样一种方式操纵免疫系统，即自身免疫的早期疾病过程将被阻止，最终目标是治愈疾病。使用小鼠恶性贫血的实验模型，其中基本病理是免疫介导的胃炎，该疾病将通过通过修饰或未成熟的抗原呈递细胞向免疫系统呈递引起疾病的自身抗原来治疗。在构成本项目背景的其他实验模型中，我们已经表明，这种方法通过产生特异性抑制免疫系统的细胞导致免疫反应的下调。在自身免疫性胃炎的研究中，我们将从皮肤、血液、脾脏和胸腺中获得修饰过的抗原提呈细胞，并利用这些细胞确定自身抗原分子提呈的最佳条件，以达到抗原特异性抑制自身免疫性胃炎的最终目的。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，而是诱导一种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治疗已建立的疾病。这是一种治疗自身免疫性胃炎的独特且具有潜在价值的策略，并提供了将这种方法应用于其他自身免疫性疾病的潜力

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