Lymphocyte Exit from Tissues: Control and Significance to Host Defense

该候选人是一位有成就的兽医，在效应T细胞贩运方面接受过广泛的研究培训。 在导师尤金布彻的指导下，候选人将加强她在实验室的实践训练 技术以及管理，沟通，演示和教学技能。额外一年 在导师实验室的培训也将用于完成淋巴细胞出口工作的一些组成部分 从周边组织以及建立模型的关键到奖项的独立阶段。 淋巴细胞从血液中迁移到组织中的特性很好，并被证明是一个关键组成部分 炎症。组织浸润可用于对抗受影响组织中的感染因子，但也可 引起破坏性的炎症性疾病，如关节炎。我们最近表明淋巴细胞 通过传入淋巴迁移出外周组织是一个受调节的主动过程， 需要CCR7的表达来实现。根据初步数据，我们现在提出，在炎症过程中， CCR7依赖性和CCR7非依赖性组织退出机制共存。我们计划识别并测试 有希望的候选出口受体，以及确定组织出口与保留的重要性， 抵御致命流感病毒感染的防御系统。候选人的长期目标需要 建立一个研究线，解决淋巴细胞浸润的调节和 对防御病原体和炎症性疾病的发展的后果。 相关性 免疫细胞进入并随后离开组织，这是发现和破坏入侵细胞的必要过程。 病原体不幸的是，免疫细胞有时会积聚在组织中， 或者它们离开组织而不破坏病原体。定义组织中的分子 了解组织出口在防御病原体中的重要性，将揭示新的控制方法， 点在调节组织炎症以及局部免疫。

The candidate is an accomplished veterinarian with extensive research training in effector T cell trafficking. With guidance of the mentor, Eugene Butcher, the candidate will enhance her training in hands-on laboratory techniques as well as managing, communication, presentation and teaching skills. An additional year of training in the mentor's lab will also be used to complete some components of the work on lymphocyte exit from peripheral tissues as well as to set up models key to the independent phase of the award. Lymphocyte migration from the blood into tissues is well characterized and proven to be a crucial component of inflammation. Tissue infiltrates can serve to fight infectious agents in the affected tissue, but can also cause destructive inflammatory diseases such as arthritis. We have recently shown that lymphocyte migration out of peripheral tissues via the afferent lymph is a regulated and active process, and that T cells require expression of CCR7 to do so. Based on preliminary data, we now propose that during inflammation, CCR7-dependent and CCR7-independent tissue exit mechanisms co-exist. We plan to identify and to test promising candidate exit receptors as well as to determine the importance of tissue exit versus retention in the defense against a lethal infection with influenza virus. The long-term goals of the candidate entail the establishment of a research line that addresses the regulation of lymphocytic infiltrates and the consequences for the defense against pathogens and the development of inflammatory diseases. Relevance Immune cells enter and subsequently leave tissues, a process necessary to find and destroy invading pathogens. Unfortunately, immune cells sometimes accumulate in tissues where they can cause tissue damage, or they leave the tissue without destroying the pathogen. Defining the molecules involved in tissue exit and knowing the importance of tissue exit in the defense against pathogens will reveal new control points in the regulation of tissue inflammation as well as local immunity.