Lymphocyte Exit from Tissues: Control and Significance to Host Defense

描述（由申请人提供）：候选人是一名熟练的兽医，在效应T细胞运输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技术以及管理，沟通，演讲和教学技能方面的培训。在导师实验室的额外一年培训也将用于完成外周组织淋巴细胞退出工作的一些组成部分，以及建立该奖项独立阶段的关键模型。 淋巴细胞从血液迁移到组织已得到充分表征，并被证明是炎症的重要组成部分。组织浸润可用于对抗受影响组织中的感染因子，但也可引起破坏性炎性疾病，如关节炎。我们最近的研究表明，淋巴细胞通过传入淋巴从外周组织中迁移出来是一个受调节的主动过程，T细胞需要CCR 7的表达才能做到这一点。基于初步数据，我们现在提出，在炎症过程中，CCR 7依赖性和CCR 7独立性组织退出机制共存。我们计划鉴定和测试有希望的候选出口受体，以及确定组织出口与保留在防御流感病毒致命感染中的重要性。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-免疫细胞进入并随后离开组织，这是发现和摧毁入侵病原体所必需的过程。不幸的是，免疫细胞有时会积聚在组织中，在那里它们会导致组织损伤，或者它们会离开组织而不破坏病原体。定义参与组织出口的分子，并了解组织出口在防御病原体中的重要性，将揭示组织炎症调节和局部免疫的新控制点。

DESCRIPTION (provided by applicant): 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.