Innate Lymphoid Cell Aging

先天性淋巴细胞老化

• 批准号: 10207444
• 负责人: Qi yang
• 金额: $ 10.83万
• 依托单位: ALBANY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2021-10-22
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10207444
• 关键词: Adoptive Transfer; Age; Aging; Antibody Response; Cell Aging; Cell Count; Cells; Communicable Diseases; Data; Development; Disease; Dose; Elderly; Goals; Host Defense; Human; Hypersensitivity; Immune; Immune system; Impairment; In Vitro; Individual; Infection; Influenza; Influenza A virus; Knockout Mice; Longevity; Lung; Lymphocyte; Lymphoid Cell; Maintenance; Molecular; Monitor; Mus; Predisposition; Public Health; Reporter; Resistance; Resistance to infection; Role; Signal Transduction; TCF Transcription Factor; Testing; Tissues; Virus Diseases; Work; aged; base; combat; conditional knockout; efficacy testing; experimental study; granulocyte; healing; immunoregulation; immunosenescence; improved; in vivo; influenza infection; insight; mouse model; novel; progenitor; response; self-renewal; stem cells; tissue regeneration; transcription factor; transcriptome sequencing

Project Summary Innate lymphoid cells (ILC) are recently discovered tissue-resident self-renewing immune cells with critical roles in barrier defense, tissue regeneration and immune regulation. Our preliminary data indicate that ILC gradually diminish in number with age. The goal of this project is to understand the cellular and molecular mechanisms that result in loss of ILC with age, and to examine whether diminished ILC numbers contribute to increased susceptibility to infections and diseases in the aged. This project focuses on group-2 innate lymphoid cells (ILC2), the predominant ILC subset in the lung. We hypothesize that decreased TCF-1 expression impairs ILC2 self-renewal and results in diminished numbers of ILC2 with age, and that diminished ILC2 responses contribute to increased susceptibility to influenza infection in the aged. We will use novel TCF- 1YFP and TCF-1 conditional knockout mice to explore the cellular and molecular mechanisms that control the longevity and self-renewal of lung-resident ILC2. We will determine whether dysregulation of such mechanisms results in loss of ILC2 with age. We will further use adoptive transfer approaches to examine whether and how diminished ILC2 responses contribute to increased susceptibility to influenza in aged mice. Finally, we will develop strategies to restore ILC2 numbers in the aged, and will test the efficacy of these strategies to enhance resistance to influenza in old mice. We anticipate that this work will provide significant insights into lymphocyte aging, and will inform strategies to improve immune defense in the elderly.

项目概要 先天淋巴细胞 (ILC) 是最近发现的组织驻留自我更新免疫细胞，具有 在屏障防御、组织再生和免疫调节中发挥关键作用。我们的初步数据表明 ILC的数量随着年龄的增长而逐渐减少。该项目的目标是了解细胞和分子 导致 ILC 随着年龄增长而丧失的机制，并检查 ILC 数量的减少是否会导致 老年人对感染和疾病的易感性增加。该项目重点关注第 2 组先天 淋巴细胞 (ILC2)，肺中主要的 ILC 亚群。我们假设 TCF-1 减少 表达会损害 ILC2 的自我更新，导致 ILC2 的数量随着年龄的增长而减少，并且这种减少 ILC2 反应导致老年人对流感感染的易感性增加。我们将使用新颖的TCF- 1YFP和TCF-1条件敲除小鼠探索控制细胞和分子机制 肺驻留 ILC2 的寿命和自我更新。我们将确定此类机制是否失调 导致 ILC2 随着年龄的增长而丧失。我们将进一步使用收养转移方法来研究是否以及如何 ILC2 反应减弱导致老年小鼠对流感的易感性增加。最后，我们将 制定恢复老年人 ILC2 数量的策略，并将测试这些策略的有效性 增强老年小鼠对流感的抵抗力。我们预计这项工作将提供重要的见解 淋巴细胞老化，并将为改善老年人免疫防御的策略提供信息。