Identifying the requirements for T cell exit from peripheral tissues during an immune response

确定免疫反应期间 T 细胞从外周组织退出的要求

• 批准号: 10649730
• 负责人: Martyna Okuniewska
• 金额: $ 4.2万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-03 至 2024-07-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10649730
• 关键词: Affect; Cell Count; Cell Line; Cells; Chronic; Cues; Ear; Enterobacteria phage P1 Cre recombinase; Environment; Goals; Homing; Hypersensitivity; Image; Immune; Immune response; Immunologic Memory; In Vitro; Infection; Inflammation; Location; Lymph; Lymphatic; Lymphatic Endothelial Cells; Lymphocyte; Memory; Modeling; Morphologic artifacts; Mus; Organ; Oxazolone; Peripheral; Phenotype; Proliferating; Role; Site; Skin; Sphingosine-1-Phosphate Receptor; Staphylococcus aureus infection; Surveys; T-Cell Activation; T-Lymphocyte; T-cell inflamed; Tamoxifen; Time; Tissues; Work; cell motility; cell type; chemokine receptor; draining lymph node; fighting; inducible Cre; inhibitor; insight; lymph nodes; lymphatic imaging; lymphatic vessel; lymphoid organ; migration; pathogen; receptor; tissue resident memory T cell; trafficking; vaccine development

Project Summary An effective immune response requires moving the right cells to the right place at the right time. T cells, an important set of immune cells, migrate extensively to fight infection. At steady state, T cells circulate among specialized organs called lymph nodes, which are found throughout the body. Pathogens and debris drain from infected tissues to local lymph nodes, and T cells survey the lymph nodes for signs of infection. After activation and proliferation in the lymph node, T cells go to the site of infection. There, they fight infection and may ultimately die, stay and form long-lived “resident memory” cells, or leave into lymphatics and recirculate. It has been shown that the chemokine receptor CCR7 brings T cells into the lymph node, while sphingosine 1-phosphate receptor 1 (S1PR1) allows them to leave. Recent studies have provided an increasingly good understanding of T cell entry into infected tissues, but exit from these tissues is still very poorly understood. The cues that guide T cell exit from inflamed tissues are important to elucidate, as they likely regulate the duration of inflammation and what kind of immune memory is generated. The goals of my work are to identify requirements for T cell exit from infected tissues, which will ultimately enable a better understanding of how T cell exit from tissues affects the immune response. In my first aim, I will assess the types of cells exiting and the role of CCR7 and S1P receptors in T cell exit from inflamed skin, and in my second aim I will assess the role of the S1P transporter SPNS2 in generating the S1P gradients that guide T cell egress from skin. My results may provide insight into strategies to limit chronic inflammation, as well as strategies to develop vaccines that generate protective resident memory T cells.

项目摘要 有效的免疫反应需要在正确的时间将正确的细胞移动到正确的位置。T细胞， 一组重要的免疫细胞，广泛迁移以对抗感染。在稳定状态下，T细胞在 被称为淋巴结节的专门器官遍布全身。病原体和泥石流 被感染的组织转移到局部淋巴结，T细胞检查淋巴结是否有感染迹象。激活后 并在淋巴结内增殖，T细胞前往感染部位。在那里，它们与感染作斗争，最终可能 死亡，停留并形成长寿的“驻留记忆”细胞，或进入淋巴管再循环。它已经被证明了 趋化因子受体CCR7将T细胞带入淋巴结，而鞘氨醇1-磷酸受体 1(S1PR1)允许他们离开。最近的研究提供了对T细胞越来越好的理解 进入受感染的组织，但离开这些组织仍然知之甚少。引导T细胞的线索 从炎症组织中退出很重要，因为它们可能调节炎症的持续时间和 会产生什么样的免疫记忆。我工作的目标是确定T细胞从 这最终将使我们能够更好地理解T细胞从组织中退出是如何影响 免疫反应。在我的第一个目标中，我将评估存在的细胞类型以及CCR7和S1P受体的作用 在我的第二个目标中，我将评估S1P转运体SPNS2在 生成引导T细胞从皮肤流出的S1P梯度。我的结果可能会为战略提供洞察力 限制慢性炎症，以及开发产生保护性常驻记忆的疫苗的策略 T细胞。