ReviewToll-like receptors in acute liver injury and regeneration

Liver is the lymphoid organ with an overwhelming innate immune system, which functions as a filter organ at the first line between the digestive tract and the rest of the body, with receiving 80% of the blood supply through portal vein. TLRs are widely expressed on parenchymal and non-parenchymal cells in the liver, which play critical roles for the liver health. Recent studies indicate that TLR-medicated signals have been involved in almost all liver diseases such as acute and chronic hepatitis, liver fibrosis and cirrhosis, alcoholic and non-alcoholic liver disease, ischemia/reperfusion liver injury, liver regeneration and hepatocellular carcinoma. In this review, the expressions of TLRs in hepatic cell populations including hepatocytes, LSECs, Kupffer cells, lymphocytes, DCs, biliary epithelial cells and HSCs, and TLR ligands and signaling in the liver are summarized. Further, recent advances in the roles of TLRs in acute liver injury and regeneration as mediator and regulator, and their potential therapeutic targets are discussed.

Research Highlights► The expressions of TLRs in hepatic cell population are specific. ► Innate immune recognition of TLRs is involved in the acute liver injury and liver regeneration. ► TLRs in immune cells play more important roles compared with liver parenchymal cells. ► TLR signaling also play important regulation on the other signals or on their families. ► TLRs are being developed for use as therapy target as well as vaccine adjuvant.