Regulation of immunity by heparan sulfate-bound IL-2

硫酸乙酰肝素结合 IL-2 对免疫的调节

• 批准号: 6614407
• 负责人: Lucile E Wrenshall
• 金额: $ 0.62万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6614407
• 关键词: T lymphocyte; apoptosis; clinical research; colitis; cytokine receptors; disease /disorder model; heparan sulfate; human subject; immunoregulation; interleukin 2; laboratory mouse; lymphocyte proliferation; protein localization; receptor binding; tissue /cell culture; transfection

DESCRIPTION (provided by applicant): Immune responses are tightly regulated to provide sufficient immunity to destroy pathogens, yet maintain control of effector populations so that autoimmunity or excessive inflammatory reactions, which might be harmful to the host, are avoided. IL-2 likely plays a significant role in this regulatory process, as it promotes either T cell death or survival depending on the physiologic state of the T cell. Preliminary data from this laboratory indicate that IL-2 is sequestered in lymphoid organs such as the spleen and thymus. Our studies also show that heparan sulfate-bound IL-2, so localized, promotes proliferation and primes cells for activation-induced cell death in vivo. These studies suggest that heparan sulfate may position IL-2 in lymphoid organs to help maintain T cell homeostasis. Using IL-2 deficient mice wherein the extracellular matrix is "reconstituted" with exogenous IL-2, the studies that follow will attempt to determine the significance of heparan sulfate-bound IL-2 to immune function. This application will seek to ascertain: (1) whether immobilization of IL-2 by heparan sulfate alters the potency of IL-2 mediated responses; (2) whether heparan sulfate-bound IL-2 differentially localizes proliferation and apoptosis in vivo; and (3) the role of heparan sulfate-bound IL-2 in an in vivo model of immune-mediated colitis. These studies will help delineate how and to what extent heparan sulfate-bound IL-2 regulates T cell homeostasis, and will lead to a better understanding of how localization of IL-2, a cytokine of major import to immune function, is modulated in vivo.

描述（由申请人提供）：免疫反应受到严格调节 提供足够的免疫力来消灭病原体，同时保持对病原体的控制 效应群体，从而导致自身免疫或过度炎症反应， 避免可能对宿主有害的情况。 IL-2 可能发挥作用 在此调节过程中发挥着重要作用，因为它促进 T 细胞死亡 或存活取决于 T 细胞的生理状态。初步数据 该实验室表明 IL-2 被隔离在淋巴器官中，例如 如脾脏和胸腺。我们的研究还表明硫酸乙酰肝素结合 IL-2 如此定位，可促进增殖并为细胞做好准备 体内激活诱导的细胞死亡。这些研究表明乙酰肝素 硫酸盐可能将 IL-2 定位在淋巴器官中以帮助维持 T 细胞 体内平衡。使用IL-2缺陷小鼠，其中细胞外基质是 用外源性 IL-2“重建”，随后的研究将尝试 确定硫酸乙酰肝素结合的 IL-2 对免疫功能的意义。 本申请将试图确定：(1) IL-2 的固定化是否通过 硫酸乙酰肝素改变 IL-2 介导的反应的效力； (2) 是否 硫酸乙酰肝素结合的 IL-2 差异定位增殖和凋亡 体内; (3) 硫酸乙酰肝素结合的 IL-2 在体内模型中的作用 免疫介导的结肠炎。这些研究将有助于描述如何以及做什么 硫酸乙酰肝素结合的 IL-2 在一定程度上调节 T 细胞稳态，并会导致 更好地了解 IL-2（一种主要细胞因子）的定位是如何定位的 对免疫功能的重要性，在体内受到调节。