MOLECULAR MECHANISMS OF THE AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME

该项目基于我们的发现，即控制淋巴细胞程序性死亡或凋亡的分子中的基因突变是导致自身免疫性淋巴细胞增殖综合征（ALPS）的原因。ALPS是一种影响儿童的疾病，导致正常淋巴细胞稳态的丧失，从而导致淋巴腺和器官肿胀。因为淋巴细胞是介导免疫反应的主要细胞，所以这种过量的淋巴细胞会导致对患者的病理性自身免疫攻击？自己的组织。在过去的一年中，我们已经确定了一种称为Fas（也称为APO-1或CD 95）的死亡诱导细胞表面受体的突变，以及对淋巴细胞程序性细胞死亡至关重要的蛋白水解酶。我们确定了患者编码的Fas受体蛋白的结构改变？通过核磁共振检测突变。这些研究有望为自身免疫性疾病的分子机制提供新的见解，并揭示淋巴细胞程序性细胞死亡途径中的关键步骤。- ALPS，细胞凋亡，杀本体调节，Fas，TNF，caspase，自身免疫，淋巴细胞-人类受试者

This project is based on our discovery that genetic mutations in molecules that control the programmed death, or apoptosis, of lymphocytes is responsible for the Autoimmune Lymphoproliferative Syndrome (ALPS). ALPS is a disease affecting children that leads to loss of normal lymphocyte homeostasis leading to swollen lymph glands and organs. Because lymphocytes are the primary cell mediating immune reactions, this excess of lymphocytes leads to a pathological autoimmune attack on the patient?s own tissues. We have identified mutations in a death-inducing cell surface receptor termed Fas (also known as APO-1 or CD95) and, in the past year, proteolytic enzymes that are crucial to lymphocyte programmed cell death. We identified the structural alterations in the Fas receptor proteins encoded by the patients? mutations by nuclear magnetic resonance. These studies promise to provide new insights into the molecular mechanisms that underlie autoimmune disease as well as revealing crucial steps in the pathway of programmed cell death in lymphocytes. - ALPS, apoptosis, propriocidal regulation, Fas, TNF, caspase, autoimmunity, lymphocyte - Human Subjects