Effects of Chronic Ethanol Exposure on Plasmacytoid DC

描述（由申请人提供）：流行病学研究一致表明，长期大量饮酒的个体与丙型肝炎病毒（HCV）感染之间存在联系。HCV能够有效逃避免疫应答的机制仍然未知。本研究旨在探讨慢性饮酒对大鼠肝脏Toll样受体（TLR）表达和肝浆细胞样（p）树突状细胞（DC）功能的影响。DC的这一亚群已引起极大的兴趣，因为它们被推测为病毒感染中的主要应答者，在刺激时产生大量的干扰素-α。对各种TLR的研究表明，通过这些受体的活化可以以不同的方式调节随后的DC反应，从而影响T细胞的活化。我们计划在培养产生的pDC和慢性酒精消耗的体外和体内模式中研究pDC上这些受体的表达和功能的改变。如果由于慢性乙醇摄入导致pDC或受体表达的发育存在缺陷，则可以通过过继转移非乙醇暴露的培养物产生的pDC来促进适当的免疫应答。

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.