权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Lung resident macrophage subsets in regulating tissue immunity - Resubmission - 1

肺驻留巨噬细胞亚群在调节组织免疫中的作用 - 重新提交 - 1

基本信息

批准号：
10544144
负责人：
Payal Damani-Yokota
金额：
$ 1.59万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
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：
2021-09-01 至 2022-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10544144
关键词：
ATAC-seq Alveolar Macrophages Animals Antiparasitic Agents Architecture Asthma Biology COVID-19 pandemic CSF1 gene CSF1R gene Cells Chromatin Chronic Obstructive Pulmonary Disease Complement 1q Cues Development Diphtheria Toxin Disease Experimental Models Flow Cytometry Frequencies Gene Expression Profile Genes Genetic Transcription Genomic approach Goals Granulocyte-Macrophage Colony-Stimulating Factor Helminths Homeostasis Hookworm Infections Human ITGAX gene Image Immune Immune response Immunity Infection Inflammation Inflammatory Response Influenza Innate Immune Response Invaded Lung Lung diseases Lymphoid Tissue Maintenance Mediating Mucous Membrane Mus Nerve Nippostrongylus Outcome Parasites Phenotype Physiological Play Population Population Heterogeneity Positioning Attribute Primary Infection Proliferating Property Pulmonary Inflammation Reporting Research Respiratory Tract Infections Role Signal Transduction Structure Testing Tissues Viral Wild Type Mouse Work Yolk Sac adaptive immune response genetic signature genome-wide human tissue in vivo in vivo Model inflammatory lung disease influenza infection insight interstitial intraperitoneal lung injury macrophage neutrophil new therapeutic target novel pathogen prevent resistin secondary infection self-renewal single-cell RNA sequencing transcriptome

项目摘要

Abstract Tissue-resident macrophages are a diverse population of cells that perform specialized functions such as sustaining tissue homeostasis and surveillance. We recently identified a novel subset of pulmonary interstitial macrophages in mice and humans that localize to the lungs and are in close contacts with the innervating nerves. These nerve and airway associated interstitial macrophages (NAMs) are transcriptionally and developmentally distinct from the alveolar macrophages (AMs). In our influenza studies, we found that NAMs proliferate robustly and their absence augmented the inflammatory response following infection. However, we know little to nothing about the functions of NAMs in type 2 immune responses. Our overall goal is to characterize the specific contributions of AMs and NAMs following infection with Nippostrongylus brasiliensis (Nb), an experimental model for type2 immunity against helminths diseases. To this end, we propose to combine multiparametric flow cytometry and imaging with our elegant in vivo models and cutting-edge genomic approaches such as scRNA-seq and ATAC-seq. The first aim of this proposal will characterize specific functions of both AMs and NAMs following an infection with Nb parasites, by using in vivo models with selective depletion of AMs or NAMs or both. In the second aim, we will investigate the mechanisms that underpin specific functions of NAMs in mounting a long-lived anti-parasitic immunity. We will also use genomic approaches to unbiasedly evaluate the chromatin accessibility of AMs and NAMs and correlating transcriptomes that allow for their critical and distinct functions. Our proposed studies will open new avenues of research and can fundamentally change our understanding of the functions and mechanisms related to pulmonary macrophages and can be extended to study other pulmonary diseases such as asthma, chronic obstructive pulmonary disease (COPD) as well as the current global pandemic COVID19.

摘要