Mobilization and trafficking of central ILC progenitors

中央 ILC 祖细胞的动员和贩运

• 批准号: 10732869
• 负责人: CHANG H KIM
• 金额: $ 30.89万
• 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: 2023-08-01 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10732869
• 关键词: Behavior; Blood Circulation; Bone Marrow; Cell Proliferation; Cells; Circadian Rhythms; Cues; Disease; Emigrations; Health; Homeostasis; Homing Behavior; IL18 gene; Immune; Immunity; Immunocompromised Host; Inflammation; Inflammatory; Inflammatory Response; Investigation; Knowledge; Longevity; Lymphocyte; Lymphoid; Lymphoid Cell; Maintenance; Mediating; Metabolic; Molecular; Natural Immunity; Organ; Outcome; Pathogenesis; Pathogenicity; Pattern; Peripheral; Population; Process; Regulation; Reporting; Role; Signal Transduction; Site; System; Testing; Therapeutic; Time; Tissues; adaptive immune response; allergic response; cell motility; chronic inflammatory disease; circadian; graft vs host disease; insight; microbial; migration; novel; novel strategies; pathogen; progenitor; receptor; stem cells; trafficking; ward

PROJECT SUMMARY Innate lymphoid cells (ILCs) are an essential part of 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. Bone marrow (BM) is the major site that produces ILC progenitors for peripheral tissues. The first step to deliver ILC progenitors into peripheral tissues is the mobilization of ILC progenitors from the 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 important questions arise in terms of the mobilization and migration of central ILC progenitors: Which progenitors dominantly emigrate from BM to generate peripheral ILC subsets? 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 underlying mechanism for the retention vs. emigration of BM ILC progenitors; Aim 2. Investigate how the retention vs. emigration of BM ILC progenitors is regulated by the circadian rhythm; Aim 3. Identify inflammatory signals that regulate the retention vs. emigration of BM ILC progenitors; Aim 4. Identify the homing behavior and trafficking receptors of emigrated ILC progenitors. The project will generate fundamental knowledge on how the peripheral ILC system is 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 先天淋巴样细胞(ILCs)是外周组织的重要组成部分，通过调节组织内环境平衡， 免疫和炎症。随着时间的推移，外周ILC人群会经历自发和诱导的磨损 并且应该被补充以保持它们的正常数量和子集组成。骨髓(BM)是 为外周组织产生ILC祖细胞的主要部位。将ILC祖细胞交付给 外周组织是骨髓中ILC祖细胞的动员，这可能需要调节 ILC祖细胞从骨髓中迁出，并最终被运送到各种外周组织。 不幸的是，我们很难理解各种ILC祖细胞是如何从BM和 在稳定状态下特征地分布到各种外周组织以及这些过程是如何 在炎症条件下改变。本项目的总体目标是了解 动员和贩运BM ILC祖细胞。 在动员和迁移国际法委员会中央祖者方面出现了几个重要问题： 哪些祖细胞主要从骨髓移居，以产生外周ILC亚群？它们是否具有多方面的潜力 和/或忠诚的祖先？触发他们移民的机制和信号是什么？做什么 血液循环中的这些祖细胞进入不同的外周组织？是迁移机制 对于每个祖细胞亚群或组织部位是通用的还是特定的？炎症信号如何改变 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.确定留存与移民的潜在机制 BM ILC祖细胞；目标2.调查BM ILC祖细胞的留存和迁出情况 由昼夜节律调节；目标3。找出调节滞留的炎症信号。 BM ILC祖细胞的迁出；目的4.确定BM ILC祖细胞的归巢行为和贩运受体 移居国外的国际法委员会的前身。该项目将产生关于外围ILC如何 系统受ILC祖细胞动员和潜在选择性运输到外周的调节 纸巾。结果将极大地提高我们对维护和管理 并将为ILC的治疗应用和控制提供新的见解 祖先。