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，作为先天抵抗力和适应性之间的桥梁 免疫力 IL-12的产生在确定免疫应答中是重要的或必需的。 保护性Th 1应答对抗感染性病原体和肿瘤，而 IL-12的过度产生可导致一系列病理性的 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 生产缺陷可导致免疫缺陷和过敏 情况，包括哮喘。 分子机制的研究 参与IL-12的产生和功能，因此对于 了解IL-12的生理作用， 蛋白质及其基因的临床应用（在感染性 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： I. IL-12 p40和p35基因表达的分子机制分析 表情; 二. 分析吞噬细胞中CD 44信号转导对IL-12的诱导作用 IL-4和IL-13对细胞分化和分泌的影响 人骨髓单核细胞和树突状细胞的促炎细胞因子 细胞; 三. 细胞因子急性诱导和激发的机制分析 通过IL-12和共刺激诱导产生。