NEUROENDOCRINE IMMUNE CONTROL OF LACRIMAL GLAND IMMUNITY

泪腺免疫的神经内分泌免疫控制

• 批准号: 2159485
• 负责人: David A. Sullivan
• 金额: $ 33.84万
• 依托单位: SCHEPENS EYE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2159485
• 关键词: Sjogren's syndrome; androgens; autoimmunity; cytokine; histochemistry /cytochemistry; hormone regulation /control mechanism; immunoglobulin A; immunologic assay /test; immunoregulation; immunosuppression; interleukin 6; laboratory mouse; laboratory rat; lacrimal apparatus; lacrimal disorder; neuroendocrine system; secretory immune system; secretory protein; tissue /cell culture; transforming growth factors

The eye's secretory immune system, which is primarily controlled by the lacrimal gland protects the ocular surface against viral, bacterial, parasitic and toxic challenge, and thereby plays a unique and crucial role in the maintenance of corneal integrity and the preservation of visual acuity. However, this immune function may be compromised by Sjogren's syndrome: this autoimmune disorder progressively destroys lacrimal tissue, and may lead to severe dry eye, intractable desiccation of the corneal epithelium, ulceration and perforation of the cornea, an increased incidence of infectious disease, and ultimately, pronounced visual impairment and blindness. The long-range objectives of this grant application are to advance our understanding of how neuroendocrinimmune factors enhance the secretory immune system of the eye, and suppress Sjogren's syndrome in the lacrimal gland. Experimental procedures involve rat and mouse models, molecular biological techniques, cell cultures, immunoassays, histochemical procedures and endocrine organ ablation and reconstitution experiments. Specific aims are: (l) To determine the mechanisms involved in the endocrine, neural and immune regulation of the ocular secretory immune system. These studies include: (a) an analysis of the neuroendocrinimmune control of secretory component and IgA transcription and synthesis in lacrimal tissue; and (b) an evaluation of the endocrine, neural and immune influence on TGF-beta1 and IL-6 production by lacrimal gland epithelial cells; and (2) To determine the role of epithelial cell cytokines in the androgen-induced suppression of autoimmune disease in lacrimal glands of a mouse model of Sjogren's syndrome. This research will examine whether androgens alter the expression and/or activity of epithelial cell cytokines (i.e. TGF-beta1, IL-6, IL-1beta and TNF-alpha), thereby causing a reduction in immunopathological lesions and an enhancement of lacrimal tissue function in Sjogren's syndrome. Results from these studies should significantly advance our knowledge of the neuroendocrinimmune regulation of mucosal immunity and autoimmunity in the lacrimal gland. In addition, findings may have health relatedness for the eye, because they: (a) examine control mechanisms underlying the ocular secretory immune system; and (b) may lead to the development of specific therapies for the clinical treatment of lacrimal gland autoimmune disease in Sjogren's syndrome.

眼睛的分泌性免疫系统，主要由 泪腺保护眼表面免受病毒，细菌， 寄生虫和有毒的挑战，从而发挥独特的和关键的作用， 在维持角膜完整性和保护视力方面， 敏锐度然而，这种免疫功能可能会受到干燥综合征的影响。 综合征：这种自身免疫性疾病逐渐破坏泪腺组织， 并可能导致严重的干眼症、角膜顽固性干燥 角膜上皮、溃疡和穿孔， 传染病的发病率，最终，明显的视觉 损伤和失明。这笔赠款的长期目标是 应用是为了促进我们对神经内分泌免疫 因子增强眼睛的分泌免疫系统，并抑制 泪腺干燥综合征。实验程序包括 大鼠和小鼠模型，分子生物学技术，细胞培养， 免疫测定、组织化学程序和内分泌器官消融， 重构实验具体目标是：（l）确定 参与内分泌、神经和免疫调节的机制， 眼分泌免疫系统这些研究包括：（a）分析 分泌成分与伊加神经内分泌免疫调控 泪腺组织中的转录和合成;和（B）评估 内分泌、神经和免疫对TGF-β 1和IL-6影响 由泪腺上皮细胞产生;和（2）为了确定 上皮细胞细胞因子在雄激素诱导的抑制卵巢癌中的作用 干燥综合征小鼠模型泪腺自身免疫性疾病 综合征这项研究将检查雄激素是否会改变 上皮细胞细胞因子（即TGF-β 1， IL-6、IL-1 β和TNF-α），从而导致 免疫病理学损伤和泪腺组织功能增强 干燥综合征的症状这些研究的结果应该显著 促进我们对粘膜的神经内分泌免疫调节的认识 泪腺的免疫和自身免疫。此外，调查结果可能 有眼睛的健康相关性，因为他们：（一）检查控制 眼分泌免疫系统的潜在机制;和（B）可导致 开发用于临床治疗的特异性疗法， 干燥综合征泪腺自身免疫性疾病