Profibrotic monocyte-derived alveolar macrophages are expanded in patients with persistent respiratory symptoms and radiographic abnormalities after COVID-19

被引：18

作者：

Bailey, Joseph I. ^{[1
]}

Puritz, Connor H. ^{[2
,3
]}

Senkow, Karolina J. ^{[1
]}

Markov, Nikolay S. ^{[1
]}

Diaz, Estefani ^{[1
]}

Jonasson, Emmy ^{[4
]}

Yu, Zhan ^{[1
]}

Swaminathan, Suchitra ^{[1
,4
]}

Lu, Ziyan ^{[1
]}

Fenske, Samuel ^{[1
]}

Grant, Rogan A. ^{[1
]}

Abdala-Valencia, Hiam ^{[1
]}

Mylvaganam, Ruben J. ^{[1
]}

Ludwig, Amy ^{[1
]}

Miller, Janet ^{[1
]}

Cumming, R. Ian ^{[5
]}

Tighe, Robert M. ^{[5
]}

Gowdy, Kymberly M. ^{[6
]}

Kalhan, Ravi ^{[1
]}

Jain, Manu ^{[1
]}

Bharat, Ankit ^{[7
,8
]}

Kurihara, Chitaru ^{[7
]}

San Jose Estepar, Ruben ^{[9
]}

San Jose Estepar, Raul ^{[9
]}

Washko, George R. ^{[10
]}

Shilatifard, Ali ^{[11
,12
]}

Sznajder, Jacob I. ^{[1
,8
]}

Ridge, Karen M. ^{[1
,8
]}

Budinger, G. R. Scott ^{[1
,8
]}

Braun, Rosemary ^{[2
,3
,13
]}

Misharin, Alexander V. ^{[1
,8
]}

Sala, Marc A. ^{[1
,8
]}

机构：

[1] Northwestern Univ, Feinberg Sch Med, Div Pulm & Crit Care Med, Chicago, IL 60208 USA

[2] Northwestern Univ, McCormick Sch Engn, Engn Sci & Appl Math, Evanston, IL USA

[3] Northwestern Univ, NSF Simons Ctr Quantitat Biol, Evanston, IL USA

[4] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Chicago, IL USA

[5] Duke Univ, Div Pulm Allergy & Crit Care Med, Sch Med, Durham, NC 27710 USA

[6] Ohio State Univ, Coll Med, Div Pulm Crit Care & Sleep Med, Columbus, OH 43201 USA

[7] Northwestern Univ, Feinberg Sch Med, Div Thorac Surg, Chicago, IL 60611 USA

[8] Northwestern Univ, Simpson Querrey Lung Inst Translat Sci, Chicago, IL 60611 USA

[9] Harvard Med Sch, Brigham & Womens Hosp, Dept Radiol, Boston, MA USA

[10] Harvard Med Sch, Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA

[11] Northwestern Univ, Feinberg Sch Med, Dept Biochem & Mol Genet, Chicago, IL 60208 USA

[12] Northwestern Univ, Simpson Querrey Inst Epigenet, Feinberg Sch Med, Chicago, IL 60611 USA

[13] Northwestern Univ, Weinberg Coll Arts & Sci, Dept Mol Biosci, Evanston, IL 60208 USA

来源：

NATURE IMMUNOLOGY | 2024年 / 25卷 / 11期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

LUNG;

D O I：

10.1038/s41590-024-01975-x

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Monocyte-derived alveolar macrophages drive lung injury and fibrosis in murine models and are associated with pulmonary fibrosis in humans. Monocyte-derived alveolar macrophages have been suggested to develop a phenotype that promotes lung repair as injury resolves. We compared single-cell and cytokine profiling of the alveolar space in a cohort of 35 patients with post-acute sequelae of COVID-19 who had persistent respiratory symptoms and abnormalities on a computed tomography scan of the chest that subsequently improved or progressed. The abundance of monocyte-derived alveolar macrophages, their gene expression programs, and the level of the monocyte chemokine CCL2 in bronchoalveolar lavage fluid positively associated with the severity of radiographic fibrosis. Monocyte-derived alveolar macrophages from patients with resolving or progressive fibrosis expressed the same set of profibrotic genes. Our findings argue against a distinct reparative phenotype in monocyte-derived alveolar macrophages, highlighting their utility as a biomarker of failed lung repair and a potential target for therapy.

引用

页码：2097 / 2109

页数：13

共 63 条

[61] SCANPY: large-scale single-cell gene expression data analysis [J].

Wolf, F. Alexander ;

Angerer, Philipp ;

Theis, Fabian J. .

GENOME BIOLOGY, 2018, 19

[62] Probabilistic harmonization and annotation of single-cell transcriptomics data with deep generative models [J].

Xu, Chenling ;

Lopez, Romain ;

Mehlman, Edouard ;

Regier, Jeffrey ;

Jordan, Michael, I ;

Yosef, Nir .

MOLECULAR SYSTEMS BIOLOGY, 2021, 17 (01)

[63]

Zaragosi L.-E., 2019, Protocols.io

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