CD127 imprints functional heterogeneity to diversify monocyte responses in inflammatory diseases

Inflammatory monocytes are key mediators of acute and chronic inflammation; yet, their functional diversity remains obscure. Single-cell transcriptome analyses of human inflammatory monocytes from COVID-19 and rheumatoid arthritis patients revealed a subset of cells positive for CD127, an IL-7 recep...

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Published inThe Journal of experimental medicine Vol. 219; no. 2
Main Authors Zhang, Bin, Zhang, Yuan, Xiong, Lei, Li, Yuzhe, Zhang, Yunliang, Zhao, Jiuliang, Jiang, Hui, Li, Can, Liu, Yunqi, Liu, Xindong, Liu, Haofei, Ping, Yi-Fang, Zhang, Qiangfeng Cliff, Zhang, Zheng, Bian, Xiu-Wu, Zhao, Yan, Hu, Xiaoyu
Format Journal Article
LanguageEnglish
Published United States Rockefeller University Press 07.02.2022
Subjects
Arthritis, Rheumatoid - immunology
COVID-19 - immunology
Epigenesis, Genetic - immunology
Female
Humans
Inflammation - immunology
Innate Immunity and Inflammation
Interleukin-7 - immunology
Interleukin-7 Receptor alpha Subunit - immunology
Male
Monocytes - immunology
SARS-CoV-2 - immunology
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Summary:Inflammatory monocytes are key mediators of acute and chronic inflammation; yet, their functional diversity remains obscure. Single-cell transcriptome analyses of human inflammatory monocytes from COVID-19 and rheumatoid arthritis patients revealed a subset of cells positive for CD127, an IL-7 receptor subunit, and such positivity rendered otherwise inert monocytes responsive to IL-7. Active IL-7 signaling engaged epigenetically coupled, STAT5-coordinated transcriptional programs to restrain inflammatory gene expression, resulting in inverse correlation between CD127 expression and inflammatory phenotypes in a seemingly homogeneous monocyte population. In COVID-19 and rheumatoid arthritis, CD127 marked a subset of monocytes/macrophages that retained hypoinflammatory phenotypes within the highly inflammatory tissue environments. Furthermore, generation of an integrated expression atlas revealed unified features of human inflammatory monocytes across different diseases and different tissues, exemplified by those of the CD127high subset. Overall, we phenotypically and molecularly characterized CD127-imprinted functional heterogeneity of human inflammatory monocytes with direct relevance for inflammatory diseases.
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B. Zhang and Yuan Zhang contributed equally to this paper.
Yuan Zhang’s present address is Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL.
Yunliang Zhang’s present address is Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Disclosures: The authors declare no competing interests exist.
Can Li’s present address is Department of Cardiology, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
ISSN:0022-1007
1540-9538
1540-9538
DOI:10.1084/jem.20211191