期刊
NATURE MEDICINE
卷 27, 期 6, 页码 1043-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41591-021-01344-3
关键词
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资金
- Short-Term EMBO Fellowship [7395]
- Helmholtz Future Inflammation and Immunology
- ERC
- EOS [SFBTR179, SFBTR 209, SFBTR1335]
- Horizon 2020
- Research Foundation Flanders [30826052]
- Deutsche Krebshilfe [70113166, 70113167]
- German-Israeli Cooperation in Cancer Research (DKFZ-MOST)
- Helmholtz-Gemeinschaft, Zukunftsthema `Immunology and Inflammation' [ZT-0027]
- Leona M. and Harry B. Helmsley Charitable Trust
- Adelis Foundation
- Pearl Welinsky Merlo Scientific Progress Research Fund
- Park Avenue Charitable Fund
- Hanna and Dr. Ludwik Wallach Cancer Research Fund
- Daniel Morris Trust
- Wolfson Family Charitable Trust
- Wolfson Foundation
- Ben B. and Joyce E. Eisenberg Foundation
- White Rose International Foundation
- Estate of Bernard Bishin for the WIS-Clalit Program
- Else Kroener Fresenius Foundation
- Jeanne and Joseph Nissim Center for Life Sciences Research
- Vainboim Family
- V. R. Schwartz Research Fellow Chair
- Swiss Society Institute for Cancer Prevention Research at the Weizmann Institute of Science, Rehovot, Israel
- European Research Council
- Israel Science Foundation
- Israel Ministry of Science and Technology
- Israel Ministry of Health
- Helmholtz Foundation
- Garvan Institute
- European Crohn's and Colitis Organization
- Deutsch-Israelische Projektkooperation
- IDSA Foundation
- Welcome Trust
- Merck KGaA, Darmstadt, Germany
- Chan Zuckerberg Initiative
- Howard Hughes Medical Institute International Scholar award
- European Research Council [724471-HemTree2.0]
- Single Cell Analysis (SCA) award of the Wolfson Foundation
- Thompson Family Foundation, a Melanoma Research Alliance Established Investigator Award [509044]
- Israel Science Foundation [703/15]
- Ernest and Bonnie Beutler Research Program for Excellence in Genomic Medicine
- Helen and Martin Kimmel award for innovative investigation
- NeuroMac DFG/Transregional Collaborative Research Center Grant
- International Progressive MS Alliance/NMSS [PA-1604 08459]
- ISF Israel Precision Medicine Program (IPMP) [607/20]
- Adelis Foundation grant
Single-cell analyses reveal cDC1 as conserved immunological drivers of non-alcoholic steatohepatitis in mice and humans. The study identified the significant role of cDC1 in NASH and confirmed their importance in liver pathology.
Single-cell analyses reveal cDC1 as conserved immunological drivers of non-alcoholic steatohepatitis in mice and humans Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are prevalent liver conditions that underlie the development of life-threatening cirrhosis, liver failure and liver cancer. Chronic necro-inflammation is a critical factor in development of NASH, yet the cellular and molecular mechanisms of immune dysregulation in this disease are poorly understood. Here, using single-cell transcriptomic analysis, we comprehensively profiled the immune composition of the mouse liver during NASH. We identified a significant pathology-associated increase in hepatic conventional dendritic cells (cDCs) and further defined their source as NASH-induced boost in cycling of cDC progenitors in the bone marrow. Analysis of blood and liver from patients on the NAFLD/NASH spectrum showed that type 1 cDCs (cDC1) were more abundant and activated in disease. Sequencing of physically interacting cDC-T cell pairs from liver-draining lymph nodes revealed that cDCs in NASH promote inflammatory T cell reprogramming, previously associated with NASH worsening. Finally, depletion of cDC1 in XCR1(DTA) mice or using anti-XCL1-blocking antibody attenuated liver pathology in NASH mouse models. Overall, our study provides a comprehensive characterization of cDC biology in NASH and identifies XCR1(+) cDC1 as an important driver of liver pathology.
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