TY  - JOUR
AU  - Deczkowska, Aleksandra
AU  - David, Eyal
AU  - Ramadori, Pierluigi
AU  - Pfister, Dominik
AU  - Safran, Michael
AU  - At The, Baoguo
AU  - Giladi, Amir
AU  - Jaitin, Diego Adhemar
AU  - Barboy, Oren
AU  - Cohen, Merav
AU  - Yofe, Ido
AU  - Gur, Chamutal
AU  - Shlomi-Loubaton, Shir
AU  - Henri, Sandrine
AU  - Suhail, Yousuf
AU  - Qiu, Mengjie
AU  - Kam, Shing
AU  - Hermon, Hila
AU  - Lahat, Eylon
AU  - Ben Yakov, Gil
AU  - Cohen-Ezra, Oranit
AU  - Davidov, Yana
AU  - Likhter, Mariya
AU  - Goitein, David
AU  - Roth, Susanne
AU  - Weber, Achim
AU  - Malissen, Bernard
AU  - Weiner, Assaf
AU  - Ben-Ari, Ziv
AU  - Heikenwälder, Mathias
AU  - Elinav, Eran
AU  - Amit, Ido
TI  - XCR1+ type 1 conventional dendritic cells drive liver pathology in non-alcoholic steatohepatitis.
JO  - Nature medicine
VL  - 27
IS  - 6
SN  - 1546-170X
CY  - New York, NY
PB  - Nature America Inc.
M1  - DKFZ-2021-01148
SP  - 1043-1054
PY  - 2021
N1  - #LA:F220#/2021 Jun;27(6):1043-1054 / #DKFZ-MOST-Ca170#
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:34017133
DO  - DOI:10.1038/s41591-021-01344-3
UR  - https://inrepo02.dkfz.de/record/168946
ER  -