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

项目摘要/摘要 这个项目的目标是了解衰老相关淋巴细胞的发育和功能。这 建议重点关注聚集在脉络丛(CP)中的第2组固有淋巴样细胞(ILC2)。 衰老。衰老是一个复杂的过程，伴随着免疫系统的深刻变化，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来对抗 着火了。我们最近的工作发现，第二组先天淋巴样细胞(ILC2)是一种组织驻留 先天淋巴细胞，聚集在老年小鼠和人的脑脊液中。这项提议的目标是 了解这些与衰老相关的先天淋巴样细胞在CP中的发育和功能。我们会 使用谱系跟踪小鼠、前体归巢试验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年龄的增长而积累的因素。我们将使用ILC2 以检测这些细胞在生理衰老中的具体作用。 最后，我们将测试增强ILC2功能是否可以缓解神经炎症和认知障碍 在阿尔茨海默病相关病理的老年小鼠中。我们预计生成的数据将提供 对免疫细胞老化机制的重大见解，并将为抗击老年病的战略提供参考 疾病。

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.