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.

项目概要/摘要 该项目的目标是了解衰老相关淋巴细胞的发育和功能。 该提案重点关注在脉络丛 (CP) 中积累的第 2 组先天淋巴细胞 (ILC2) 衰老是一个复杂的过程，与免疫系统的深刻变化相关。 适应性免疫功能恶化（免疫衰老）和炎症增加 （令人惊讶的是，一些免疫细胞亚群也具有抗炎和修复功能。 随着衰老而积累，这可能代表一种保护性负反馈机制来对抗 我们最近的工作发现，2 类先天淋巴细胞 (ILC2) 是一种组织驻留细胞。 先天淋巴细胞在老年小鼠和人类的 CP 中积累。该提案的目标是 了解 CP 中这些与衰老相关的先天淋巴细胞的发育和功能。 使用谱系追踪小鼠、前体归巢试验和过继转移来检查发育 我们将使用 ILC2 来研究这些细胞的起源并探索导致它们积累的因素。 缺陷小鼠和 ILC2 诱导缺失小鼠，以检查这些细胞在生理衰老中的具体作用。 最后，我们将测试ILC2功能是否可以缓解神经炎症和认知障碍 我们预计生成的数据将提供患有阿尔茨海默病相关病理的老年小鼠的结果。 对免疫细胞衰老机制的重要见解，并将为对抗老年病的策略提供信息 疾病。