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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

基本信息

批准号：
6883956
负责人：
Lucile E Wrenshall
金额：
$ 23.85万
依托单位：
UNIVERSITY OF NEBRASKA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-04-15 至 2007-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6883956
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

项目摘要

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）：免疫应答受到严格调节，提供足够的免疫力来消灭病原体，同时保持对因此自身免疫或过度炎症反应，这可能对宿主有害。IL-2可能发挥作用，在这一调节过程中起重要作用，因为它促进T细胞死亡，或存活取决于T细胞的生理状态。初步数据表明IL-2被隔离在淋巴器官中，如脾脏和胸腺。我们的研究还表明，硫酸乙酰肝素结合如此定位的IL-2促进细胞增殖并引发细胞增殖。体内活化诱导的细胞死亡。这些研究表明，硫酸盐可以将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"，随后的研究将试图确定硫酸乙酰肝素结合的IL-2对免疫功能的意义。本申请将寻求确定：（1）通过免疫抑制剂固定IL-2是否是有效的。硫酸乙酰肝素改变IL-2介导的应答的效力;（2）是否硫酸乙酰肝素结合的IL-2对增殖和凋亡的差异定位（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阐明如何以及如何硫酸乙酰肝素结合的IL-2调节T细胞稳态的程度，为了更好地理解IL-2的定位，一种主要的细胞因子，输入到免疫功能，在体内被调节。