Project Details
Projekt
The role of type 1 dendritic cells (cDC1) in the pathogenesis of non-alcoholic steatohepatitis
Subject Area
Gastroenterology
Term
from 2018 to 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 411345524
Non-alcoholic fatty liver (NAFL) is the hepatic consequence of metabolic syndrome and can progress to non-alcoholic steatohepatitis (NASH). The identification of molecular and cellular factors that determine the progression of NASH and lead to irreversible hepatocellular damage are crucial. Dendritic cells (DCs) play a significant role in immunity and tolerance and represent a heterogeneous cell population involving three main subsets: conventional type 1 (cDC1), type 2 (cDC2) and plasmacytoid DCs (pDCs). The applicant’s laboratory has identified cDC1 cells as key players in the progression of NASH. Accordingly, metabolic challenge of Batf3-/- animals (Basic Leucine Zipper Transcription Factor, ATF-Like-3) that lack cDC1 subtype of DCs resulted in the progression of steatosis towards steatohepatitis, manifesting in increased influx of inflammatory cells into the liver and elevated inflammatory cytokine production of myeloid cells upon innate stimuli. Thus, cDC1s represent a protective DC subtype that influences the pro-anti-inflammatory balance and protects the liver from metabolic damage. Here, we aim to clarify what functional and genetic features are associated with cDC1s in the various stage of disease progression and what molecular and cellular characteristics of these cells mediate protection in murine NASH. Moreover, as one of the safeguard of liver integrity, we aim to test the therapeutic capacity of cDC1s as cellular therapy and/or during in situ manipulation of this cellular compartment during established NASH.
DFG Programme
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