Immuno-pathophysiology of Lymphocytic Foci in Sjogren?s Syndrome

干燥综合征淋巴细胞病灶的免疫病理生理学

• 批准号: 8321067
• 负责人: Cuong Q Nguyen
• 金额: $ 24.19万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8321067
• 关键词: Affect; Animal Model; Autoantigens; Autoimmune Diseases; Autoimmune Process; B-Lymphocytes; Biological; Biopsy; Bladder; Cells; Cephalic; Chronic; Clinical; Connective Tissue Diseases; Data; Dementia; Development; Disease; Disease Progression; Disease susceptibility; Exhibits; Exocrine Glands; Fatigue; Foundations; Frequencies; Functional disorder; Future; Gene Rearrangement; Genetic; Gland; Goals; Gonadal Steroid Hormones; Grant; Human; Hypergammaglobulinemia; Impaired cognition; Individual; Interleukin-17; Kidney; Labial Salivary Gland; Lacrimal gland structure; Lead; Lung; Lymphocyte; Manuscripts; Memory Loss; Mental disorders; Natural Killer Cells; Neuropathy; Organ; Patients; Peripheral; Phase; Population; Preparation; Publications; Rheumatoid Factor; Role; Salivary Glands; Sensory; Serum; Sjogren' s Syndrome; Skin; Solid; Symptoms; Syndrome; T-Cell Receptor; T-Lymphocyte; Testing; Therapeutic; Time; Vagina; Woman; Xerostomia; abstracting; base; cell type; cytokine; design; gene therapy; genetic profiling; interleukin-22; men; mouse model; new technology; novel; prevent; response; sexual dimorphism; single cell analysis; vector

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.

干燥综合征（SjS）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， 特别是唾液腺和泪腺它可以通过影响包括胃肠道在内的其他器官而成为全身性疾病。 管道、皮肤、肺、脉管系统、肾脏、膀胱和阴道。肌肉组织受累会导致 纤维肌痛样症状和慢性疲劳。大约20%的患者发生各种 神经病，包括感觉、外周、颅和脊髓神经病，表现为认知功能障碍。 例如痴呆、注意力不集中、记忆力丧失和各种精神障碍。作为 与许多自身免疫性结缔组织病一样，女性SjS存在性别二型性， 比男性多10到20倍，这表明性激素在疾病中的作用 易感性或进展。SjS在人类和动物模型中的一个独特特征是形成 唾液腺和泪腺中的淋巴细胞病灶（LF）。虽然其中一个更主要的细胞 浸润腺体的细胞群是产生IL-17和IL-22细胞因子的致病性THI 7细胞， 已知分泌这些细胞因子的浸润细胞的频率以及它们的基因谱， 单个T细胞受体。使用一种称为微雕刻的新技术， 分析，这项研究的目的是提供一个概念的证据，在检查个人TH 17细胞产生IL-22。 为了实现这一目标，将进行两个具体目标：1）表征单个IL-22分泌细胞 浸润SjS患者的唇唾液腺（LSG），和2）鉴定T细胞受体（TCR）-P基因 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，将建立用于鉴定和表征单个T细胞的概念证明， 相应的TCR-0基因重排和分泌产物。