SALIVARY GLAND DYSFUNCTION IN AUTOIMMUNE NOD MICE

唾液腺功能障碍是由饮食改变，放射治疗， 衰老、某些药物和病毒或遗传疾病。 的损失 腺体功能和由此产生的唾液导致临床上 表现为口干或“口干”。“一些自身免疫性疾病， 男性，例如，干燥综合征和1型糖尿病（IDD），显示 唾液腺进行性淋巴细胞浸润， 随后唾液合成和分泌减少。 IDD是 其特征在于自身免疫性破坏胰岛素产生β细胞， 胰腺 进一步的研究表明，糖尿病患者 患者和NOD（非肥胖糖尿病）小鼠，淋巴细胞浸润 包括下颌下腺在内的外分泌组织的损伤是很常见的。 一 人类自身免疫性IDD的代谢并发症是口干症， 龋齿和潜在牙周病的相关增加 发展 到目前为止，开发一个适当的动物模型， 分析自身免疫诱导的唾液腺功能障碍将有助于 对口干症的研究。 使用NOD小鼠，我们最近观察到， 伴随着针对β细胞、淋巴细胞的进行性自身免疫反应 同时浸润到腮腺和下颌下腺 糖尿病和糖尿病前期动物。 与此同时， 刺激流速下降和特定分泌蛋白丢失 生物合成能力 这些观察结果表明，唾液腺 功能障碍不是由于急性炎症反应引起的， 淋巴细胞浸润和细胞破坏，但更准确地说， 反映了由于慢性淋巴细胞活化而引起的变化， 自身免疫病理学 因此，我们建议在这里调查 NOD小鼠的自身免疫性涎腺炎，以确定其作为 用于自身免疫诱导的口干症的动物模型。 具体来说，我们计划 1)描述针对唾液腺的自身免疫反应， 口干症; 2）确定膜受体水平的变化， 信号转导途径的细胞内成分， 通常在分泌过程中被激活，3）表征 胰岛素样肽在腮腺炎发病时对腮腺功能的作用 IDD中的自身免疫性涎腺炎。 这些研究的结果应该提供 对自身免疫反应的深入了解， 具有明显临床和牙科相关性的腺体功能障碍。 在 此外，我们预计NOD小鼠将被证明是一个有用的模型 发展了我们对干燥综合征，风湿性关节炎， 和1型IDD;其中自身免疫病理学引起的免疫功能丧失的疾病。 保护性唾液分泌物，导致患者不适 与口腔干燥和龋齿增加，牙周病和 口腔粘膜和软组织恶化。

Salivary gland dysfunction results from dietary changes, radiation therapy, aging, certain medications and viral or genetic diseases. The loss of gland function and thus saliva production results in the clinical manifestation of xerostomia or "dry mouth." Some autoimmune diseases of man, for example, Sjogrens syndrome and Type 1 diabetes (IDD), show progressive lymphocytic infiltration of the salivary glands with a subsequent reduction in saliva synthesis and secretion. IDD is characterized by autoimmune destruction of insulin producing beta cells of the pancreas. Further investigations have revealed that in diabetic patients and the NOD (non-obese diabetic) mouse, lymphocytic infiltration of exocrine tissues, including the submandibular gland, is common. One metabolic complication of human autoimmune IDD is xerostomia with associated increases in caries and potential periodontal disease development. To date, development of an adequate animal model for the analysis of autoimmune induced salivary gland dysfunction would facilitate the study of xerostomia. Using the NOD mouse, we recently observed that with the progressive autoimmune reaction against beta cells, lymphocytes simultaneously infiltrated into the parotid and submandibular glands of diabetic and pre-diabetic animals. This was accompanied by a corresponding decline in stimulated flow rates and loss of specific secretory protein biosynthetic capacity. These observations suggest that salivary gland dysfunction is not due to an acute inflammatory response caused by lymphocytic infiltration and cellular destruction, but more accurately reflects changes due to the chronic lymphocytic activation present in the autoimmune pathology. Therefore, we propose here to investigate the autoimmune sialoadenitis of the NOD mouse to determine its potential as an animal model for autoimmune-induced xerostomia. Specifically, we plan to 1) Characterize the autoimmune reaction against salivary glands leading to xerostomia; 2) Determine changes in the level of membrane receptors and intracellular components of the signal transduction pathways which are commonly activated during the secretory process and 3) Characterize the role of insulin-like peptides on parotid gland function at onset of autoimmune sialoadenitis in IDD. Results from these studies should provide insights into autoimmune responses that traditionally lead to salivary gland dysfunction with obvious clinical and dental relevance. In addition, we anticipate that the NOD mouse will prove to be a useful model for developing our understanding of Sjogrens syndrome, Rheumatoid arthritis and Type 1 IDD; diseases in which the autoimmune pathology causes a loss of protective salivary secretions with the resulting patient discomfort associated with xerostomia and increased caries, periodontal disease and aggravation of oral mucosa and soft tissue.