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.
CD127 imprints functional heterogeneity to diversify monocyte responses in inflammatory diseases
Disclosures: The authors declare no competing interests exist.
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.
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.
- Award Id(s): 31725010,31821003,31991174,32030037
- Award Id(s): 2020YFA0509100
- Award Id(s): 2020NCPZX01
- Award Id(s): 2020Z99CFZ024
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Bin Zhang, Yuan Zhang, Lei Xiong, Yuzhe Li, Yunliang Zhang, Jiuliang Zhao, Hui Jiang, Can Li, Yunqi Liu, Xindong Liu, Haofei Liu, Yi-Fang Ping, Qiangfeng Cliff Zhang, Zheng Zhang, Xiu-Wu Bian, Yan Zhao, Xiaoyu Hu; CD127 imprints functional heterogeneity to diversify monocyte responses in inflammatory diseases. J Exp Med 7 February 2022; 219 (2): e20211191. doi: https://doi.org/10.1084/jem.20211191
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