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: 6332238
• 负责人: Lucile E Wrenshall
• 金额: $ 5.02万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-15 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6332238
• 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; 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（申请人提供）：免疫反应严格调节 提供足够的免疫力来破坏病原体，但保持控制 效应人群以使自身免疫性或过度炎症反应， 可能会避免对主机有害。 IL-2可能扮演 在此调节过程中的重要作用，因为它促进了T细胞死亡 或根据T细胞的生理状态生存。初步数据 从该实验室表明IL-2在淋巴器官中隔离 作为脾脏和胸腺。我们的研究还表明，硫酸乙酰肝素结合 IL-2如此局部，促进了增殖和质数细胞 激活诱导的体内细胞死亡。这些研究表明乙酰肝素 硫酸盐可以在淋巴机器人器官中定位IL-2，以帮助维持T细胞 稳态。使用IL-2缺乏小鼠，其中细胞外基质为 用外源IL-2“重构”，随后的研究将尝试 确定乙酰硫酸盐结合的IL-2对免疫功能的重要性。 该申请将寻求确定：（1）是否将IL-2固定 硫酸乙酰肝素改变IL-2介导的反应的效力； （2）是否 乙酰硫酸乙酰肝素结合的IL-2差异定位了增殖和凋亡 体内; （3）乙par硫酸盐结合的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如何处理 范围硫酸乙酰肝素结合的IL-2调节T细胞稳态，并将领导 可以更好地了解主要的细胞因子IL-2的定位 导入免疫功能，在体内调节。