Mobilization and trafficking of central ILC progenitors

中央 ILC 祖细胞的动员和贩运

• 批准号: 10766537
• 负责人: CHANG H KIM
• 金额: $ 14.84万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-09 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10766537
• 关键词: Behavior; Blood; Blood Circulation; Bone Marrow; Bone Tissue; Cells; Circadian Rhythms; Circulation; Common Lymphoid Progenitor; Compensation; Cues; Destinations; Development; Disease; Emigrations; Health; Homeostasis; IL18 gene; Immune; Immunity; Inflammation; Inflammatory; Inflammatory Response; Infusion procedures; Knowledge; Lymphocyte; Lymphoid; Lymphoid Cell; Maintenance; Mediating; Metabolic; Organ; Outcome; Pathogenicity; Pattern; Peripheral; Physiological; Play; Population; Process; Regulation; Role; Signal Transduction; Site; System; Testing; Therapeutic; Time; Tissues; adaptive immune response; allergic response; behavior change; circadian; hematopoietic tissue; insight; microbial; migration; novel; novel strategies; pathogen; progenitor; programs; receptor; stem cells; trafficking; ward

PROJECT SUMMARY ILCs play essential roles in peripheral tissues by regulating tissue homeostasis, immunity and inflammation. Peripheral ILC populations undergo spontaneous and induced attrition over time and should be replenished to maintain their normal numbers and subset composition. The first step to deliver ILC progenitors into peripheral tissues is the mobilization of ILC progenitors from the central hematopoietic tissue, bone marrow (BM), and this presumably requires regulated emigration of ILC progenitors from the BM and their ultimate trafficking into various peripheral tissues. Unfortunately, we hardly understand how various ILC progenitors are mobilized from the BM and characteristically distributed to various peripheral tissues in steady state and how these processes are altered in inflammatory conditions. The overarching objective of this project is to understand the mobilization and trafficking of BM ILC progenitors. Several key questions arise in terms of the mobilization and migration of central ILC progenitors: Which progenitors dominantly emigrate from BM to generate peripheral ILC subsets in steady state? Are they multi- potential and/or committed progenitors? What are the mechanisms and signals that trigger their emigration? How do these progenitor cells in the blood circulation enter distinct peripheral tissues? Is the migration mechanism universal or specific for each progenitor subset or tissue site? How do inflammatory signals alter the mobilization and migration patterns of ILC progenitors, and can we control tissue ILC activity in pathogenic conditions by utilizing mobilized BM ILC progenitors or targeting their mobilization and migration? We devised the following specific aims to investigate these questions regarding the mobilization and trafficking of ILC progenitors. Aim 1. Identify the mechanism that mobilizes central ILC progenitors in steady state; Aim 2. Identify the mechanism by which central ILC progenitors are mobilized in inflammatory conditions; Aim 3. Identify potentially diverse mechanisms for the entrance of mobilized ILC progenitors into distinct peripheral tissues. The project will generate fundamental knowledge on how the peripheral ILC system is maintained and regulated by the mobilization and potentially selective trafficking of ILC progenitors into peripheral tissues. The outcomes will greatly enhance our understanding of the maintenance and regulation of peripheral ILCs and will provide novel insights into therapeutic utilization and control of ILC progenitors.

项目总结 ILCs通过调节组织内环境平衡、免疫和炎症，在外周组织中发挥重要作用。 随着时间的推移，外周ILC人群会经历自发和诱导的磨损，应该补充到 保持它们的正常数量和子集组成。将ILC祖细胞移植到外周血细胞的第一步 组织是从中央造血组织，即骨髓(BM)动员ILC祖细胞，这是 据推测，需要将国际法委员会的祖先从BM规范地移民出去，并最终将他们贩运到 各种外周组织。不幸的是，我们很难理解各种ILC的前身是如何 从骨髓中动员，并在稳定状态下特征地分布到各种周围组织 以及这些过程在炎症条件下是如何改变的。这样做的首要目标是 该项目旨在了解BM ILC祖细胞的动员和贩运情况。 在动员和迁移国际法委员会中央祖者方面出现了几个关键问题： 祖细胞主要从骨髓中迁出，在稳定状态下产生外周ILC亚群？他们是不是多个- 潜在的和/或忠诚的祖先？触发他们移民的机制和信号是什么？ 血液循环中的这些祖细胞是如何进入不同的外周组织的？是迁移 每个祖细胞亚群或组织部位的机制是通用的还是特定的？炎症信号是如何改变的 ILC祖细胞的动员和迁移模式以及我们能否控制组织中ILC的活性 通过利用动员的BM ILC祖细胞还是针对其动员和迁移来改善条件？ 我们制定了以下具体目标来调查这些关于动员和 贩运国际法委员会的祖细胞。目标1.确定动员中央ILC祖细胞的机制 稳定状态；目标2.确定中央ILC前体细胞在 炎症条件；目标3.确定动员的人进入的潜在不同机制 ILC祖细胞分化为不同的外周组织。该项目将产生关于如何 外围ILC系统通过动员和潜在的选择性贩运维持和管理 ILC祖细胞进入外周组织。这些结果将极大地加深我们对 外周ILC的维持和调节，将为治疗提供新的见解 ILC祖细胞的利用和控制。