XCR1+ type 1 conventional dendritic cells drive liver pathology in non-alcoholic steatohepatitis - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Nature Medicine Année : 2021

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

Sandrine Henri
Hila Hermon
Achim Weber

Résumé

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.

Domaines

Immunologie
Fichier principal
Vignette du fichier
nash.pdf (3.03 Mo) Télécharger le fichier
Origine Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-03234079 , version 1 (20-01-2022)

Identifiants

Citer

Aleksandra Deczkowska, Eyal David, Pierluigi Ramadori, Dominik Pfister, Michael Safran, et al.. XCR1+ type 1 conventional dendritic cells drive liver pathology in non-alcoholic steatohepatitis. Nature Medicine, 2021, ⟨10.1038/s41591-021-01344-3⟩. ⟨hal-03234079⟩
1284 Consultations
1619 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More