%0 Journal Article
%A Deczkowska, Aleksandra
%A David, Eyal
%A Ramadori, Pierluigi
%A Pfister, Dominik
%A Safran, Michael
%A At The, Baoguo
%A Giladi, Amir
%A Jaitin, Diego Adhemar
%A Barboy, Oren
%A Cohen, Merav
%A Yofe, Ido
%A Gur, Chamutal
%A Shlomi-Loubaton, Shir
%A Henri, Sandrine
%A Suhail, Yousuf
%A Qiu, Mengjie
%A Kam, Shing
%A Hermon, Hila
%A Lahat, Eylon
%A Ben Yakov, Gil
%A Cohen-Ezra, Oranit
%A Davidov, Yana
%A Likhter, Mariya
%A Goitein, David
%A Roth, Susanne
%A Weber, Achim
%A Malissen, Bernard
%A Weiner, Assaf
%A Ben-Ari, Ziv
%A Heikenwälder, Mathias
%A Elinav, Eran
%A Amit, Ido
%T XCR1+ type 1 conventional dendritic cells drive liver pathology in non-alcoholic steatohepatitis.
%J Nature medicine
%V 27
%N 6
%@ 1546-170X
%C New York, NY
%I Nature America Inc.
%M DKFZ-2021-01148
%P 1043-1054
%D 2021
%Z #LA:F220#/2021 Jun;27(6):1043-1054 / #DKFZ-MOST-Ca170#
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:34017133
%R 10.1038/s41591-021-01344-3
%U https://inrepo02.dkfz.de/record/168946