The development and function of aging-associate innate lymphoid cells in the choroid plexus

脉络丛中衰老相关先天淋巴细胞的发育和功能

• 批准号: 10659515
• 负责人: Qi yang
• 金额: $ 186.13万
• 依托单位: RUTGERS BIOMEDICAL AND HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10659515
• 关键词: Adoptive Transfer; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease patient; Amphiregulin; Anti-Inflammatory Agents; B-Lymphocytes; Biological Assay; Blocking Antibodies; Bone Marrow; Cell Aging; Cell Lineage; Cell physiology; Cells; Clustered Regularly Interspaced Short Palindromic Repeats; Complex; Data; Dementia; Deterioration; Development; Disease; Elderly; Endothelium; Exhibits; Family; Feedback; Gene Deletion; Goals; Homing; Human; Immune; Immune system; Impaired cognition; Impairment; In Vitro; Inflammaging; Inflammation; Interleukin-5; Lymphocyte; Lymphoid; Lymphoid Cell; Mediating; Molecular; Mus; Output; Pathology; Physiological; Population; Process; Property; Proteins; Reporting; Role; Structure of choroid plexus; Techniques; Testing; Tissues; Work; aged; aging brain; cognitive function; combat; disorder prevention; human old age (65+); immune function; immunosenescence; improved; insight; knockout gene; mouse model; neuroinflammation; neuroprotection; novel; novel strategies; repair function

Project Summary/Abstract The goal of this project is to understand the development and function of aging-associate lymphocytes. This proposal focuses on group 2 innate lymphoid cells (ILC2) that accumulate in the choroid plexus (CP) with aging. Aging is a complicated process associated with profound changes in the immune system, characterized by both a deterioration of adaptive immune function (immunosenescence) and also increased inflammation (inflammaging). Suprisingly, some immune cell subsets with anti-inflammatory and reparative function also accumulate with aging, which might represent a protective negative feedback mechanism to counter inflammaging. Our recent work discovers that group-2 innate lymphoid cells (ILC2), a type of tissue-resident innate lymphocytes, accumulate in the CP of aged mice and humans. The goal of this proposal is to understand the development and function of these aging-associated innate lymphoid cells in the CP. We will use lineage tracking mice, precursor homing assay, and adoptive transfer to examine the developmental origins of these cells and to explore the factors that lead to their accumulation with aging. We will use ILC2 deficient and ILC2 inducible-deletion mice to examine the specific role of these cells in physiological aging. Finally, we will test whether enhancing ILC2 function can alleviate neuroinflammation and cognitive impairment in aged mice with Alzheimer’s disease associated pathologies. We expect that the data generated will provide significant insights into the mechanisms of immune cell aging, and will inform strategies to combat geriatric diseases.

项目总结/摘要 本研究的目的是了解衰老相关淋巴细胞的发育和功能。这 一项提案的重点是第2组先天性淋巴细胞（ILC 2），它在脉络丛（CP）中积累， 衰老衰老是一个复杂的过程，与免疫系统的深刻变化有关，其特征是 由于适应性免疫功能（免疫衰老）的恶化和炎症的增加， （发炎）。令人惊讶的是，一些具有抗炎和修复功能的免疫细胞亚群也 随着年龄的增长而积累，这可能代表了一种保护性的负反馈机制， 发炎我们最近的工作发现，第2组先天淋巴样细胞（ILC 2），一种组织驻留细胞， 先天性淋巴细胞在老年小鼠和人类的CP中积累。本提案的目的是 了解CP中这些衰老相关先天淋巴细胞的发育和功能。我们将 使用谱系跟踪小鼠，前体归巢测定和过继转移来检查发育 这些细胞的起源，并探索导致它们随着衰老而积累的因素。我们将使用ILC 2 缺陷型和ILC 2诱导缺失型小鼠，以检查这些细胞在生理衰老中的特定作用。 最后，我们将测试增强ILC 2功能是否可以减轻神经炎症和认知障碍。 老年痴呆症相关病理的小鼠。我们预计，生成的数据将提供 对免疫细胞衰老机制的重要见解，并将为对抗老年病的战略提供信息。 疾病