Immune mechanisms behind NAFLD-associated inflammation

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide and a significant contributor to liver cirrhosis, transplantation, and hepatocellular carcinoma.
PUBLISHED IN: Journal of Hepatology 2022

Comment:

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide and a significant contributor to liver cirrhosis, transplantation, and hepatocellular carcinoma. In an attempt to characterise its underlying inflammatory mechanisms and generate novel therapies, single-cell RNA sequencing and high-dimensional multi-omics have recently been put to the test, with the former permitting the exceptional characterisation of immune cell heterogeneity in NAFLD-associated inflammation.

The aim of this review is to summarise recent inflammation-related discoveries pertaining to NAFLD. It examines the role of immune cell subsets at different disease stages and proposes an integrative model of hepatic inflammatory pathways and extrahepatic, inflammatory triggers.

Key learnings:

NAFLD’s pathogenesis combines metabolic dysregulation, fibrogenesis, and progressive inflammation. The latter is regulated by intrahepatic factors, including lipid accumulation and oxidative stress, as well as extrahepatic factors (e.g., adipose tissue inflammation, and the gut-liver axis). Furthermore, novel findings have identified embryonic Kupffer cells as the potential instigators of non-alcoholic steatohepatitis (NASH). Importantly, conventional dendritic cells (cDCs), particularly cDC1, have been found to be elevated in NAFLD patients, and their frequency correlated with NASH severity. Recent studies also highlight auto-aggressive CD8 T cells characterised by tissue residency (CXCR6) and exhaustion (PD-1) markers as attackers of steatotic hepatocytes. Lastly, emerging findings underscore the inflammatory role of platelets in early NAFLD, which aggregate in the liver during steatosis.

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Dr. S Duarte

Dr. S Duarte

Articles: 56

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