Lymphocyte Exit from Tissues: Control and Significance to Host Defense

候选人是一位经验丰富的兽医，在效应器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，候选人将加强她在动手实验室的培训 技术以及管理、沟通、演示和教学技能。额外的一年 导师实验室的培训也将用于完成淋巴细胞退出工作的某些部分 以及建立对奖项的独立阶段至关重要的模型。 淋巴细胞从血液迁移到组织的特征很好，并且被证明是至关重要的组成部分。 发炎的症状。组织浸润物可以用来对抗受影响组织中的传染病，但也可以 导致破坏性的炎症性疾病，如关节炎。我们最近发现，淋巴细胞 通过传入淋巴从周围组织中迁移出来是一个受调节和活跃的过程，而T细胞 需要CCR7的表达才能这样做。根据初步数据，我们现在提出，在炎症期间， CCR7依赖和非CCR7依赖的组织退出机制共存。我们计划识别并测试 有希望的候选退出受体，以及确定组织退出与保留的重要性 对致命的流感病毒感染的防御。候选人的长期目标需要 建立一条研究路线，解决淋巴细胞渗入的调节和 对病原体的防御和炎症性疾病的发展的后果。 相关性 免疫细胞进入和随后离开组织，这是发现和摧毁入侵所必需的过程 病原体。不幸的是，免疫细胞有时会聚集在组织中，在那里它们可以引起组织 破坏，或者在不破坏病原体的情况下离开组织。定义组织中涉及的分子 了解组织出口在防御病原体中的重要性将揭示新的控制措施 在调节组织炎症和局部免疫方面的要点。

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.