NEUROENDOCRINE IMMUNE CONTROL OF LACRIMAL GLAND IMMUNITY

眼睛的分泌免疫系统，主要由 泪腺保护眼睛表面免受病毒，细菌， 寄生和有毒的挑战，从而发挥着独特和关键的作用 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Sjogren的损害 综合征：这种自身免疫性疾病会逐渐破坏泪道组织， 并可能导致严重的干眼，难治性的角膜干燥 角膜上皮、溃疡和穿孔，增加 传染病的发病率，并最终明显的视觉 损伤和失明。这笔赠款的长期目标 应用是为了加深我们对神经内分泌免疫如何 增强眼睛的分泌免疫系统的因素，并抑制 泪腺干燥综合征。实验程序包括 大鼠和小鼠模型，分子生物技术，细胞培养， 免疫分析、组织化学程序和内分泌器官切除 重建实验。具体目标是：(L)确定 参与内分泌、神经和免疫调节的机制 眼部分泌性免疫系统。这些研究包括：(A)分析 分泌成分与免疫球蛋白A的神经内分泌免疫调控 泪液组织中的转录和合成；和(B)评价 内分泌、神经和免疫对转化生长因子-β1和白介素6的影响 泪腺上皮细胞产生；和(2)测定 上皮性细胞因子在雄激素诱导的血管内皮细胞抑制中的作用 干燥小鼠泪腺自身免疫性疾病 综合症。这项研究将考察雄激素是否会改变 上皮细胞细胞因子(即转化生长因子-β1， IL-6、IL-1β和肿瘤坏死因子-α)，从而导致 免疫病理损害与泪道组织功能的增强 患有干燥综合征。这些研究的结果应该显著地 提高对粘膜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 与眼睛的健康相关，因为他们：(A)检查对照 眼睛分泌免疫系统的潜在机制；和(B)可能导致 致力于临床治疗的特定疗法的发展 干燥综合征中的泪腺自身免疫性疾病。

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.