Immuno-pathophysiology of Lymphocytic Foci in Sjogren?s Syndrome

干燥综合征是一种以外分泌腺功能障碍为主要特征的自身免疫性疾病。 具体地说，是唾液腺和泪腺。它可以是全身性的，通过影响包括Gl在内的其他器官 肠道、皮肤、肺、血管、肾脏、膀胱和阴道。肌肉系统的参与可以导致 肌萎缩侧索硬化症和慢性疲劳。大约20%的患者会发展成不同的 神经病，包括感觉神经病、外周神经病、颅神经病和脊髓病，表现为认知 例如痴呆症、注意力不集中、记忆力减退和各种精神障碍。AS 由于许多自身免疫性结缔组织疾病，女性Sjs存在性别二型性。 受影响的频率是男性的10到20倍，这表明性激素在疾病中发挥了作用 易感性或进行性。在人类和动物模型中，Sjs的一个独特特征是形成 唾液和泪腺的淋巴细胞性病灶(LF)。尽管其中一个更具优势的细胞 渗入腺体的是致病的Thi 7细胞，它们产生IL-17和IL-22细胞因子，很少是 已知分泌这些细胞因子的浸润性细胞的频率和它们的基因图谱 单个T细胞受体。使用一种名为微雕的新技术，专为单细胞设计 分析，这项研究的目的是在检查产生IL-22的单个TH17细胞时提供概念证明。 为了实现这一目标，将实现两个具体目标：1)确定单个IL-22分泌细胞的特征 2)T细胞受体(TCR)-P基因的鉴定 SjS患者LSG中单个IL-22分泌细胞的重排拟议研究的结果， 因此，将建立概念证明，以识别和表征单个T细胞及其 相应的TCR-0基因重排和分泌产物。

Sjogren's syndrome (SjS) is an autoimmune disease characterized primarily by exocrine gland dysfunction, specifically, the salivary and lacrimal glands. It can be systemic by affecting other organs including the Gl tract, skin, lungs, vasculature, kidneys, bladder and vagina. Involvement of the musculature can lead to flbromyalgla-llke symptoms and chronic fatigue. Approximately 20% of patients develop various neuropathies, including sensory, peripheral, cranial and myelopathic neuropathies exhibited by cognitive impairments such as dementia, lack of concentration, memory loss and various psychiatric disorders. As with many autoimmune connective tissue diseases, there exists a sexual dimorphism in SjS with women affected 10- to 20-times more frequently than men, suggesting a role for sex hormones in disease susceptibility or progression. A unique feature of SjS in both humans and animal models Is the formation of lymphocytic focus (LF) in the salivary and lacrimal glands. Although one of the more predominant cell populations infiltrating the glands is the pathogenic THI 7 cells that produce IL-17 and IL-22 cytokines, little is known about frequencies of infiltrating cells secreting these cytokines and the genetic profiles of their individual T cell receptors. Using a novel technology called microengraving designed for single cell analysis, this study aims to provide a proof of concept in examining individual TH17 cells that produce IL-22. To achieve this goal, two specific aims will be carried out: 1) characterizing individual IL-22-secretlng cells infiltrating the labial salivary glands (LSG) of SjS patients, and 2) identifying the T cell receptor (TCR)-P gene rearrangement of Individual IL-22 secreting cells in LSG of SjS patients. Results of the proposed study, therefore, will establish proof of concept for identification and characterization of individual T cells with their corresponding TCR-0 gene rearrangement and secreted products.