IMMUNOBIOLOGY OF INTERLUKIN-12

INTERLUKIN-12 的免疫生物学

• 批准号: 2761165
• 负责人: GIORGIO TRINCHIERI
• 金额: $ 31.55万
• 依托单位: WISTAR INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-05-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2761165
• 关键词: B lymphocyte; CD44 molecule; T lymphocyte; biological signal transduction; cell differentiation; colony stimulating factor; dendritic cells; gene expression; human subject; interferon gamma; interleukin 12; interleukin 13; interleukin 4; laboratory mouse; leukocyte activation /transformation; molecular cloning; monocyte; neoplastic cell; protein biosynthesis; tissue /cell culture; tumor necrosis factor alpha

IL-12 is a central player in the regulation of inflammation and immunity, serving as a bridge between innate resistance and adaptive immunity. IL-12 production is important or essential in determining the protective Th1 response against infectious pathogens and tumors, whereas overproduction of IL-12 can result in a series of pathological manifestations, including systemic inflammatory response syndrome, organ-specific autoimmunity, sarcoidosis, vascular lesions, whereas defective production can result in immunodeficiency and allergic situations, including asthma. The study of the molecular mechanisms involved in IL-12 production and function is thus important for the understanding of the physiological role of IL-12 and for the planning of the clinical use of the protein and its genes (in infectious diseases, tumors, severe allergy, or as adjuvants in vaccination) or of antagonists of its production and activity (in autoimmunity, sarcoidosis, etc.). To this end, we propose to: I. Analyze the molecular mechanisms of IL-12 p40 and p35 gene expression; II. Analyze the induction of IL-12 by CD44 signaling in phagocytic cells and the effect of IL-4 and IL-13 on differentiation and production of proinflammatory cytokines by human myelomonocytic and dendritic cells; III. Analyze the mechanisms of acute induction and priming for cytokine production induced by IL-12 and costimulation.

IL-12 是炎症调节的核心参与者 免疫力，作为先天抵抗和适应性之间的桥梁 免疫。 IL-12 的产生对于确定 针对传染性病原体和肿瘤的保护性 Th1 反应，而 IL-12过度产生可导致一系列病理 表现，包括全身炎症反应综合征， 器官特异性自身免疫、结节病、血管病变，而 生产缺陷可能导致免疫缺陷和过敏 情况，包括哮喘。 分子机制研究 因此，参与 IL-12 的产生和功能对于 了解 IL-12 的生理作用并进行规划 蛋白质及其基因的临床应用（在传染性 疾病、肿瘤、严重过敏或作为疫苗接种的佐剂）或 其产生和活性的拮抗剂（在自身免疫中， 结节病等）。 为此，我们建议： 一、分析IL-12 p40和p35基因的分子机制 表达; 二. 分析吞噬细胞中 CD44 信号传导对 IL-12 的诱导 细胞以及 IL-4 和 IL-13 对分化和生产的影响 人骨髓单核细胞和树突状细胞促炎细胞因子的作用 细胞； 三． 分析细胞因子的急性诱导和启动机制 IL-12 和共刺激诱导产生。