| First Author | Deczkowska A | Year | 2021 |
| Journal | Nat Med | Volume | 27 |
| Issue | 6 | Pages | 1043-1054 |
| PubMed ID | 34017133 | Mgi Jnum | J:335309 |
| Mgi Id | MGI:7444583 | Doi | 10.1038/s41591-021-01344-3 |
| Citation | Deczkowska A, et al. (2021) XCR1(+) type 1 conventional dendritic cells drive liver pathology in non-alcoholic steatohepatitis. Nat Med 27(6):1043-1054 |
| abstractText | 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. |
