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Liver-centered multi-organ crosstalk between bone marrow, adipose tissue, gut, and brain has been shown to involve in various liver diseases, ranging from alcoholic liver disease, steatohepatitis, and fibrosis. Our lab demonstrates pathogenic mechanism of liver disease in these aspects, which may shed a new light on novel therapeutic treatment development.
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The bone marrow-liver axis
Apart from the tissue-resident immune cells in the liver, bone marrow derived immune cells mature, proliferate, and egress into the bloodstream in response to cytokine gradient. Migrated bone marrow cells have been shown to provide protective effects and ameliorate impaired liver functions in cirrhotic patients by bone marrow cell transplantation.
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The adipose tissue-liver axis
Metabolic and genetic changes, especially adipokines, in adipocytes and enterocytes affect steatosis and inflammation of the liver. Reciprocally, hepatocytes and non-parenchymal cells in the liver influence adipogenesis, lipolysis, and inflammation of adipose tissue.
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The gut-liver axis
Gut-liver crosstalk is mainly triggered by the influx of PAMPs via the portal vein due to increased gut permeability. Under this condition, Kupffer cells and macrophages are recruited, leading to the production of pro-inflammatory cytokines and chemokines. Various signaling pathways, such as NF-kB and TLR pathways will then be activated, resulting in hepatic injury and fibrosis.
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