Details

Autor(en) / Beteiligte

• Deczkowska, Aleksandra
• David, Eyal
• Ramadori, Pierluigi
• Pfister, Dominik
• Safran, Michal
• Li, Baoguo
• Giladi, Amir
• Jaitin, Diego Adhemar
• Barboy, Oren
• Cohen, Merav
• Yofe, Ido
• Gur, Chamutal
• Shlomi-Loubaton, Shir
• Henri, Sandrine
• Suhail, Yousuf
• Qiu, Mengjie
• Kam, Shing
• Hermon, Hila
• Lahat, Eylon
• Ben Yakov, Gil
• Cohen-Ezra, Oranit
• Davidov, Yana
• Likhter, Mariya
• Goitein, David
• Roth, Susanne
• Weber, Achim
• Malissen, Bernard
• Weiner, Assaf
• Ben-Ari, Ziv
• Heikenwälder, Mathias
• Elinav, Eran
• Amit, Ido

Titel

XCR1+ type 1 conventional dendritic cells drive liver pathology in non-alcoholic steatohepatitis

Ist Teil von

• Nature Medicine, 2021-06, Vol.27 (6), p.1043-1054

Ort / Verlag

New York: Nature Publishing Group US

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. Single-cell analyses reveal cDC1 as conserved immunological drivers of non-alcoholic steatohepatitis in mice and humans