Effects of Chronic Ethanol Exposure on Plasmacytoid DC

慢性乙醇暴露对浆细胞样 DC 的影响

• 批准号: 6836659
• 负责人: AUDREY H LAU
• 金额: $ 4.36万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-13 至 2008-09-12
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6836659
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse; antigen presentation; cellular pathology; clinical research; dendritic cells; immunosuppression; laboratory mouse; liver cells; passive immunization; predoctoral investigator; receptor expression; tissue /cell culture; toll like receptor; toxicology

DESCRIPTION (provided by applicant): Epidemiological studies have consistently shown a linkage between individuals who chronically consume significant amounts of alcohol and hepatitis C viral (HCV) infection. The mechanism by which HCV is able to efficiently evade immune responses is still unknown. It is the purpose of this proposal to study the effects of chronic alcohol consumption on the expression of Toll-like receptors (TLR) and the function of hepatic plasmacytoid (p) dendritic cells (DC). This subset of DC has become of great interest as they are speculated to be primary responders in viral infection, producing large amounts of interferon-alpha upon stimulation. Studies on various TLR have shown that activation through these receptors can modulate the subsequent DC response in a distinct manner and thus influence the activation of T cells. We plan to investigate alterations in the expression and function of these receptors on pDC in established in vitro and in vivo mode s of culture-generated pDC and chronic alcohol consumption. If there are defects in the development of pDC or receptor expression as a result of chronic ethanol intake, it may be possible to promote an appropriate immune response through adoptive transfer of non-ethanol exposed culture-generated pDC.

描述（由申请人提供）：流行病学研究始终显示出长期消耗大量酒精和丙型肝炎病毒（HCV）感染的个体之间的联系。 HCV能够有效逃避免疫反应的机制仍然未知。该提案的目的是研究慢性酒精消耗对收费受体（TLR）表达的影响以及肝浆细胞类动物（P）树突状细胞（DC）的功能。 DC的这一子集已引起人们的极大兴趣，因为它们被推测是病毒感染中的主要反应者，在刺激时会产生大量的干扰素-α。对各种TLR的研究表明，通过这些受体的激活可以以不同的方式调节后续的直流反应，从而影响T细胞的激活。我们计划研究这些受体在培养生成的PDC和长期饮酒的体外和体内模式中这些受体在PDC上的表达和功能的改变。如果由于慢性乙醇的摄入而导致PDC或受体表达的发展存在缺陷，则可能通过非乙醇暴露的培养培养基生成的PDC来促进适当的免疫反应。