CD127 imprints functional heterogeneity to diversify monocyte responses in inflammatory diseases

Zhang，Bin1,2; Zhang，Yuan1,2; Xiong，Lei3; Li，Yuzhe4; Zhang，Yunliang1,2; Zhao，Jiuliang5; Jiang，Hui5; Li，Can5; Liu，Yunqi1,2; Liu，Xindong6; Liu，Haofei6; Ping，Yi Fang6; Zhang，Qiangfeng Cliff3,7; Zhang，Zheng8,9; Bian，Xiu Wu6; Zhao，Yan5; Hu，Xiaoyu1,2,7,10

2022-02-07

10.1084/jem.20211191

The Journal of experimental medicine   影响因子和分区

1540-9538

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.

英语

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其他

IMMUNOLOGY

2-s2.0-85123461465

Scopus

1.Institute for Immunology and School of Medicine,Tsinghua University,China
2.Beijing Key Laboratory for Immunological Research on Chronic Diseases,China
3.Ministry of Education Key Laboratory of Bioinformatics,Beijing Advanced Innovation Center for Structural Biology,Center for Synthetic and Systems Biology,School of Life Sciences,Tsinghua University,China
4.Academy for Advanced Interdisciplinary Studies,Peking University,China
5.Department of Rheumatology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,National Clinical Research Center for Dermatologic and Immunological Diseases,China
6.Institute of Pathology,Southwest Hospital,Third Military Medical University (Army Medical University),China
7.Tsinghua-Peking Center for Life Sciences,China
8.Institute for Hepatology,National Clinical Research Center for Infectious Disease,Shenzhen Third People's Hospital,Shenzhen,China
9.Second Affiliated Hospital,School of Medicine,Southern University of Science and Technology,Shenzhen,China
10.Center for Human Disease Immuno-monitoring,Beijing Friendship Hospital,China

Zhang，Bin,Zhang，Yuan,Xiong，Lei,et al. CD127 imprints functional heterogeneity to diversify monocyte responses in inflammatory diseases[J]. The Journal of experimental medicine,2022,219(2).

Zhang，Bin.,Zhang，Yuan.,Xiong，Lei.,Li，Yuzhe.,Zhang，Yunliang.,...&Hu，Xiaoyu.(2022).CD127 imprints functional heterogeneity to diversify monocyte responses in inflammatory diseases.The Journal of experimental medicine,219(2).

Zhang，Bin,et al."CD127 imprints functional heterogeneity to diversify monocyte responses in inflammatory diseases".The Journal of experimental medicine 219.2(2022).