IMMUNOTOXIC EFFECTS OF IODINE

碘的免疫毒性作用

• 批准号: 2684196
• 负责人: Carol Lynne Burek
• 金额: $ 19.41万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 2001-03-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2684196
• 关键词: NOD mouse; T lymphocyte; autoantibody; autoimmune disorder; autoimmune thyroiditis; cellular immunity; clinical research; cytokine; dietary mineral; disease /disorder model; disease /disorder proneness /risk; genetic disorder; human subject; immunopathology; immunotoxicity; iodination; iodine; molecular pathology; nutrition related tag; pathogenic diet; thyroglobulin; tissue /cell culture

DESCRIPTION: (Adapted from the investigator's Abstract) Autoimmune thyroiditis is a multifactorial condition with several genetic and environmental components contributing to disease. Iodine has been implicated as one of these components. The broad long-term objectives remain to explore the immunotoxic of iodine in autoimmune thyroiditis (AT). Increased environmental exposure to iodine from dietary or therapeutic sources may contribute to the increasing prevalence of AT in humans. Both animal models of thyroiditis and clinical observations in humans relate ingestion of excess iodine as a potent risk factor in subjects genetically predisposed to AT. However, the pathogenic mechanism has not been determined. The investigator's hypothesis is that excess ingested iodine leads to highly iodinated Tg, and that the highly iodinated Tg is a more potent auto-immunogen than poorly-iodinated Tg in subjects predisposed to AT. As a new direction from their current research on humans, they will use a mouse model as the primary test system to study the role of iodine in triggering the expression of AT. The congenic mutant strain of NOD mice (NOD.B10.A (4R)-H2-H4) do not get diabetes but do get thyroiditis that is exacerbated by dietary iodine. The investigator will continue to study the role of iodinated Tg in humans using in vitro cell techniques. The specific aims for this proposal are: 1. To show that ingested iodine promotes AT in the NOD mouse model and establish basic and immunological parameters. The investigator will study the effect of iodine dose, timing, age, sex, on disease induction, on phenotype of cells in the thyroid. He will determine the frequency of these cells and then relate these findings to their cytokine and antibody profiles. 2. To induce thyroiditis in vivo. He will show that T cells from mice with lesions after a high iodine diet will transfer disease into non-affect recipients, first, with spleen cells from iodine-treated mice, then iodinated Tg to support the hypothesis. Individual parameters of the immune system will be monitored as for specifics aim 1. 3. To show in human studies that T cell clones preferentially recognize highly iodinated Tg greater than poorly iodinated Tg, to establish frequency of these cells by limiting dilution and determine their cytokine profiles in order to relate these findings to disease. The mouse model permits mechanistic research of dietary iodine that is closely analogous to humans and allows experimental procedures that cannot be done in humans. If the mechanism of disease can be clarified, then the potential exists for developing strategies to abrogate the deleterious immune response.

描述：(改编自《研究人员摘要》)自身免疫 甲状腺炎是一种多因素的疾病，有几种遗传性和 导致疾病的环境因素。碘一直是 被牵连为这些组成部分之一。宏大的长期目标 探讨碘在自身免疫性甲状腺炎(AT)中的免疫毒性作用。 通过饮食或治疗增加环境中的碘暴露 来源可能是人类AT患病率增加的原因之一。两者都有 人类甲状腺炎动物模型及临床观察 摄入过量碘是遗传性受试者的潜在危险因素 倾向于AT。然而，其致病机制尚不清楚。 下定决心。研究人员的假设是摄入过量的碘 导致高碘甘油三酯，而高碘甘油三酯 易感人群中比低碘甘油三酯更强的自身免疫原 在…。作为他们目前对人类研究的一个新方向，他们将使用 以小鼠模型为主要测试系统来研究碘在体内的作用 触发AT的表达。NOD小鼠的同源突变株 (NOD.B10.A(4R)-H2-H4)不会得糖尿病，但会得甲状腺炎 饮食中的碘加剧了这一现象。调查员将继续研究 用体外细胞技术研究碘化甘油三酯在人体中的作用。具体的 这项提议的目的是：1.证明摄入的碘促进AT 建立NOD小鼠模型，建立基本免疫学参数。这个 研究人员将研究碘剂量、时间、年龄、性别对 疾病诱导，对甲状腺细胞表型的影响。他会决定 这些细胞的频率，然后将这些发现与其 细胞因子和抗体图谱。2.体内诱发甲状腺炎。他会的 表明高碘饮食后受损小鼠的T细胞将 首先，通过脾细胞将疾病转移到未受影响的接受者 碘处理的小鼠，然后对甘油三酯进行碘标记以支持这一假说。 免疫系统的个别参数将被监测，如 特效药的目标是1.3。在人类研究中表明T细胞克隆 优先识别高碘甘油三酯大于低碘甘油三酯 Tg，通过限制稀释建立这些细胞的频率并确定 他们的细胞因子图谱，以便将这些发现与疾病联系起来。这个 小鼠模型允许对饮食碘进行密切的机理研究 类似于人类，允许不能完成的实验程序 在人类身上。如果疾病的机制能够被澄清，那么潜在的 存在着开发策略以消除有害免疫的存在 回应。