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| 005 | 20251110150742.0 | ||
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| 100 | 1 | _ | |a Deczkowska, Aleksandra |0 0000-0003-0844-4346 |b 0 |
| 245 | _ | _ | |a XCR1+ type 1 conventional dendritic cells drive liver pathology in non-alcoholic steatohepatitis. |
| 260 | _ | _ | |a New York, NY |c 2021 |b Nature America Inc. |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1762783646_2549712 |2 PUB:(DE-HGF) |x Review Article |
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| 500 | _ | _ | |a #LA:F220#/2021 Jun;27(6):1043-1054 / #DKFZ-MOST-Ca170# |
| 520 | _ | _ | |a 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 XCR1DTA 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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| 700 | 1 | _ | |a David, Eyal |b 1 |
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| 700 | 1 | _ | |a Safran, Michael |b 4 |
| 700 | 1 | _ | |a At The, Baoguo |b 5 |
| 700 | 1 | _ | |a Giladi, Amir |b 6 |
| 700 | 1 | _ | |a Jaitin, Diego Adhemar |b 7 |
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| 700 | 1 | _ | |a Cohen, Merav |b 9 |
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| 700 | 1 | _ | |a Henri, Sandrine |0 0000-0002-8980-9193 |b 13 |
| 700 | 1 | _ | |a Suhail, Yousuf |b 14 |
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| 700 | 1 | _ | |a Hermon, Hila |b 17 |
| 700 | 1 | _ | |a Lahat, Eylon |b 18 |
| 700 | 1 | _ | |a Ben Yakov, Gil |b 19 |
| 700 | 1 | _ | |a Cohen-Ezra, Oranit |b 20 |
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| 700 | 1 | _ | |a Likhter, Mariya |b 22 |
| 700 | 1 | _ | |a Goitein, David |b 23 |
| 700 | 1 | _ | |a Roth, Susanne |b 24 |
| 700 | 1 | _ | |a Weber, Achim |0 0000-0003-0073-3637 |b 25 |
| 700 | 1 | _ | |a Malissen, Bernard |0 0000-0003-1340-9342 |b 26 |
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