Inflammation Mediated by JNK in Myeloid Cells Promotes the Development of Hepatitis and Hepatocellular Carcinoma

•JNK in myeloid cells promotes hepatic infiltration by inflammatory cells•Myeloid cell JNK deficiency suppresses development of fulminant hepatitis•JNK in myeloid cells promotes the development of hepatocellular carcinoma

SummaryThe cJun NH2-terminal kinase (JNK) signaling pathway is required for the development of hepatitis and hepatocellular carcinoma. A role for JNK in liver parenchymal cells has been proposed, but more recent studies have implicated non-parenchymal liver cells as the relevant site of JNK signaling. Here, we tested the hypothesis that myeloid cells mediate this function of JNK. We show that mice with myeloid cell-specific JNK deficiency exhibit reduced hepatic inflammation and suppression of both hepatitis and hepatocellular carcinoma. These data identify myeloid cells as a site of pro-inflammatory signaling by JNK that can promote liver pathology. Targeting myeloid cells with a drug that inhibits JNK may therefore provide therapeutic benefit for the treatment of inflammation-related liver disease.

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