首页|Type Ⅰ interferon signaling facilitates resolution of acute liver injury by priming macrophage polarization

Type Ⅰ interferon signaling facilitates resolution of acute liver injury by priming macrophage polarization

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Due to their broad functional plasticity,myeloid cells contribute to both liver injury and recovery during acetaminophen overdose-induced acute liver injury(APAP-ALI).A comprehensive understanding of cellular diversity and intercellular crosstalk is essential to elucidate the mechanisms and to develop therapeutic strategies for APAP-ALI treatment.Here,we identified the function of IFN-I in the myeloid compartment during APAP-ALI.Utilizing single-cell RNA sequencing,we characterized the cellular atlas and dynamic progression of liver CD11b+cells post APAP-ALI in WT and STAT2 T403A mice,which was further validated by immunofluorescence staining,bulk RNA-seq,and functional experiments in vitro and in vivo.We identified IFN-I-dependent transcriptional programs in a three-way communication pathway that involved IFN-I synthesis in intermediate restorative macrophages,leading to CSF-1 production in aging neutrophils that ultimately enabled Trem2+ restorative macrophage maturation,contributing to efficient liver repair.Overall,we uncovered the heterogeneity of hepatic myeloid cells in APAP-ALI at single-cell resolution and the therapeutic potential of IFN-I in the treatment of APAP-ALI.

APAP-ALIIFN-IMacrophage polarizationscRNA-seqSTAT2 T403 phosphorylationCSF1+ neutrophil

Qiaoling Song、Shyamasree Datta、Xue Liang、Xiaohan Xu、Paul Pavicic、Xiaonan Zhang、Yuanyuan Zhao、Shan Liu、Jun Zhao、Yuting Xu、Jing Xu、Lihong Wu、Zhihua Wu、Minghui Zhang、Zhan Zhao、Chunhua Lin、Yuxin Wang、Peng Han、Peng Jiang、Yating Qin、Wei Li、Yingying Zhang、Yonglun Luo、Ganes Sen、George R.Stark、Chenyang Zhao、Thomas Hamilton、Jinbo Yang

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Key Laboratory of Marine Drugs,Ministry of Education,School of Medicine and Pharmacy,Ocean University of China,Qingdao,China

Department of Inflammation and Immunity,Lerner Research Institute,Cleveland Clinic Foundation,Cleveland,OH,USA

Lars Bolund Institute of Regenerative Medicine,Qingdao-Europe Advanced Institute for Life Sciences,BGI-Qingdao,BGI-Shenzhen,Shenzhen,China

Innovation Center of Marine Drug Screening&Evaluation,Qingdao National Laboratory for Marine Science and Technology,Qingdao,China

Department of Radiation,Affiliated Hospital of Qingdao University,Qingdao,China

Department of Urology,Yantai Yuhuangding Hospital,Yantai,China

Department of Cancer Biology,Lerner Research Institute,Cleveland Clinic Foundation,Cleveland,OH,USA

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Key R&D Program of Shandong ProvinceShandong Provincial Key Laboratory Platform ProjectMajor Program of National Natural Science Foundation of China

2020CXGC0105032021ZDSYS1181991525

2023

10.1038/s41423-022-00966-y

中国免疫学杂志(英文版)
中国免疫学会

中国免疫学杂志(英文版)

CSTPCDCSCDSCI
影响因子：0.731
ISSN：1672-7681
年,卷(期)：2023.20(2)
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