Journal Article (Review Article)

DKFZ-2021-01148

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png XCR1+ type 1 conventional dendritic cells drive liver pathology in non-alcoholic steatohepatitis.

Deczkowska, A. ; David, E. ; Ramadori, P.DKFZ* ; Pfister, D.DKFZ* ; Safran, M. ; At The, B. ; Giladi, A. ; Jaitin, D. A. ; Barboy, O. ; Cohen, M. ; Yofe, I. ; Gur, C. ; Shlomi-Loubaton, S. ; Henri, S. ; Suhail, Y. ; Qiu, M. ; Kam, S.DKFZ* ; Hermon, H. ; Lahat, E. ; Ben Yakov, G. ; Cohen-Ezra, O. ; Davidov, Y. ; Likhter, M. ; Goitein, D. ; Roth, S. ; Weber, A. ; Malissen, B. ; Weiner, A. ; Ben-Ari, Z. ; Heikenwälder, M.DKFZ* ; Elinav, E. (Last author)DKFZ* ; Amit, I.

2021
Nature America Inc. New York, NY

This record in other databases:  

Please use a persistent id in citations: doi:10.1038/s41591-021-01344-3

Abstract: 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.

Note: #LA:F220#/2021 Jun;27(6):1043-1054 / #DKFZ-MOST-Ca170#

---

Contributing Institute(s):

1. Chronische Entzündung und Krebs (F180)
2. Mikrobiom und Krebs (F220)

Research Program(s):

1. 316 - Infektionen, Entzündung und Krebs (POF4-316) (POF4-316)

Appears in the scientific report 2021

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 30 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---