Innate Lymphoid Cell Aging

先天性淋巴细胞老化

基本信息

批准号：
10531485
负责人：
Qi yang
金额：
$ 22.38万
依托单位：
RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-30 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10531485
关键词：
Innate Lymphoid Cell Aging

项目摘要

Project Summary/Abstract Under this administrative supplement, we propose to examine impact of innate lymphoid cell aging on the disease outcome of SARS-CoV-2 infection, by adding COVID-19 to the parent study which examines the innate lymphoid cell aging during influenza infection. The aged population is particularly susceptible to COVID-19. It is estimated that more than 80% of individuals who have died from COVID-19 in the U.S. are elderly individuals ≥ 65 years old. The underlying mechanisms remain unclear. Aging is associated drastic and complicated changes in the immune system. Aging is associated drastic and complicated changes in the immune system. The mucosal barrier sites harbor unique subsets of innate and innate-like lymphocytes implicated in host defense, tissue homeostasis, and tissue repair. Our published and preliminary data indicate that the long-lived lung-resident innate/innate-like lymphocytes, such as ILC2 and MAIT cells, undergo tremendous changes with aging. We hypothesize that impaired function of mature lung ILC2 underpins tissue damage and inflammation observed during SARS-CoV-2 infection with aging, and that boosting the activity of ILC2 will increase host resistance and tolerance to severe COVID-19 in the elderly individuals. We have recently established a mouse model of SARS-CoV-2 infection in aged mice. We will further characterize this mouse model, and will use this model to test whether enhancing ILC2 activity will increase host resistance and tolerance resistance to COVID-19 in aged mice. We have available for this study a CDC approved full functioning ABSL3 lab. This supplement will directly address multiple objectives related to the goals outlined in the COVID-19 notice of special interest. This supplement will develop aged animal models suitable for studies on pathogenesis of SARS-CoV-2 infection in the aging context. The proposal experiments will also elucidate how cellular and molecular mechanisms of aging impact the treatment, recovery, and repair of tissue and organ systems during SARS-CoV-2 infection.

项目摘要/摘要在这种行政补充下，我们建议检查先天淋巴样细胞的影响通过向父母添加COVID-19的SARS-COV-2感染疾病结果衰老研究在影响力感染过程中检查先天淋巴样细胞衰老的研究。老年人人口特别容易受到COVID-19的影响。据估计，超过80％在美国死于Covid-19的个人年龄在美国年龄段≥65岁。这潜在机制尚不清楚。衰老是相关的急剧变化免疫系统。衰老是免疫的急剧变化和复杂的变化系统。粘膜屏障站点藏有先天和先天淋巴细胞的独特子集在宿主防御，组织稳态和组织修复中实施。我们出版和初步数据表明，长寿的肺居民先天/先天性淋巴细胞，例如ILC2和 Mait细胞随着衰老而发生巨大变化。我们假设在SARS-COV-2中观察到的组织损伤和炎症是成熟的肺ILC2的基础衰老感染，增强ILC2活性的感染将增加宿主电阻和老年人对严重的covid-19的耐受性。我们最近建立了一只鼠标老年小鼠SARS-COV-2感染的模型。我们将进一步表征该鼠标模型，并将使用此模型来测试增强ILC2活性是否会增加宿主电阻和对年龄小鼠的耐受性耐受性。我们为这项研究提供了CDC 批准的全功能ABSL3实验室。该补充将直接解决多个目标与共同兴趣通知书中概述的目标有关的目标有关。这种补充会开发了适合研究SARS-COV-2感染发病机理的老年动物模型衰老的环境。建议实验还将阐明细胞和分子衰老的机制影响组织和器官系统的治疗，恢复和修复在SARS-COV-2感染期间。