A vasculature-resident innate lymphoid cell population in mouse lungs

Abstract Tissue-resident immune cells such as innate lymphoid cells (ILC) are known to reside in the parenchymal compartments of tissues and modulate local immune protection. Here we use intravascular cell labeling, parabiosis and multiplex 3D imaging to identify a population of group 3 ILCs in mice...

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Main Authors: Simon Shirley, Hiroshi Ichise, Vincenzo Di Natale, Jiacheng Jin, Christine Wu, Raymond Zou, Wanwei Zhang, Yinshan Fang, Yingyu Zhang, Miao Chen, Sophia Peng, Uttiya Basu, Jianwen Que, Yuefeng Huang
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-58982-1
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author Simon Shirley
Hiroshi Ichise
Vincenzo Di Natale
Jiacheng Jin
Christine Wu
Raymond Zou
Wanwei Zhang
Yinshan Fang
Yingyu Zhang
Miao Chen
Sophia Peng
Uttiya Basu
Jianwen Que
Yuefeng Huang
author_facet Simon Shirley
Hiroshi Ichise
Vincenzo Di Natale
Jiacheng Jin
Christine Wu
Raymond Zou
Wanwei Zhang
Yinshan Fang
Yingyu Zhang
Miao Chen
Sophia Peng
Uttiya Basu
Jianwen Que
Yuefeng Huang
author_sort Simon Shirley
collection DOAJ
description Abstract Tissue-resident immune cells such as innate lymphoid cells (ILC) are known to reside in the parenchymal compartments of tissues and modulate local immune protection. Here we use intravascular cell labeling, parabiosis and multiplex 3D imaging to identify a population of group 3 ILCs in mice that are present within the intravascular space of lung blood vessels (vILC3). vILC3s are distributed broadly in alveolar capillary beds from which inhaled pathogens enter the lung parenchyma. By contrast, conventional ILC3s in tissue parenchyma are enriched in lymphoid clusters in proximity to large veins. In a mouse model of pneumonia, Pseudomonas aeruginosa infection results in rapid vILC3 expansion and production of chemokines including CCL4. Blocking CCL4 in vivo attenuates neutrophil recruitment to the lung at the early stage of infection, resulting in prolonged inflammation and delayed bacterial clearance. Our findings thus define the intravascular space as a site of ILC residence in mice, and reveal a unique immune cell population that interfaces with tissue alarmins and the circulating immune system for timely host defense.
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spelling doaj-art-769e309cf8124ad0863e60a952ff23dd2025-08-20T02:17:48ZengNature PortfolioNature Communications2041-17232025-04-0116111710.1038/s41467-025-58982-1A vasculature-resident innate lymphoid cell population in mouse lungsSimon Shirley0Hiroshi Ichise1Vincenzo Di Natale2Jiacheng Jin3Christine Wu4Raymond Zou5Wanwei Zhang6Yinshan Fang7Yingyu Zhang8Miao Chen9Sophia Peng10Uttiya Basu11Jianwen Que12Yuefeng Huang13Department of Microbiology & Immunology, Columbia University Medical CenterLymphocyte Biology Section, Laboratory of Immune Systems Biology, National Institute of Allergy and Infectious Disease, National Institutes of HealthDepartment of Microbiology & Immunology, Columbia University Medical CenterDepartment of Microbiology & Immunology, Columbia University Medical CenterDepartment of Microbiology & Immunology, Columbia University Medical CenterDepartment of Microbiology & Immunology, Columbia University Medical CenterDepartment of Microbiology & Immunology, Columbia University Medical CenterDepartment of Medicine, Columbia Center for Human Development, Columbia University Medical CenterDepartment of Microbiology & Immunology, Columbia University Medical CenterDepartment of Microbiology & Immunology, Columbia University Medical CenterDepartment of Microbiology & Immunology, Columbia University Medical CenterDepartment of Microbiology & Immunology, Columbia University Medical CenterDepartment of Medicine, Columbia Center for Human Development, Columbia University Medical CenterDepartment of Microbiology & Immunology, Columbia University Medical CenterAbstract Tissue-resident immune cells such as innate lymphoid cells (ILC) are known to reside in the parenchymal compartments of tissues and modulate local immune protection. Here we use intravascular cell labeling, parabiosis and multiplex 3D imaging to identify a population of group 3 ILCs in mice that are present within the intravascular space of lung blood vessels (vILC3). vILC3s are distributed broadly in alveolar capillary beds from which inhaled pathogens enter the lung parenchyma. By contrast, conventional ILC3s in tissue parenchyma are enriched in lymphoid clusters in proximity to large veins. In a mouse model of pneumonia, Pseudomonas aeruginosa infection results in rapid vILC3 expansion and production of chemokines including CCL4. Blocking CCL4 in vivo attenuates neutrophil recruitment to the lung at the early stage of infection, resulting in prolonged inflammation and delayed bacterial clearance. Our findings thus define the intravascular space as a site of ILC residence in mice, and reveal a unique immune cell population that interfaces with tissue alarmins and the circulating immune system for timely host defense.https://doi.org/10.1038/s41467-025-58982-1
spellingShingle Simon Shirley
Hiroshi Ichise
Vincenzo Di Natale
Jiacheng Jin
Christine Wu
Raymond Zou
Wanwei Zhang
Yinshan Fang
Yingyu Zhang
Miao Chen
Sophia Peng
Uttiya Basu
Jianwen Que
Yuefeng Huang
A vasculature-resident innate lymphoid cell population in mouse lungs
Nature Communications
title A vasculature-resident innate lymphoid cell population in mouse lungs
title_full A vasculature-resident innate lymphoid cell population in mouse lungs
title_fullStr A vasculature-resident innate lymphoid cell population in mouse lungs
title_full_unstemmed A vasculature-resident innate lymphoid cell population in mouse lungs
title_short A vasculature-resident innate lymphoid cell population in mouse lungs
title_sort vasculature resident innate lymphoid cell population in mouse lungs
url https://doi.org/10.1038/s41467-025-58982-1
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