CXCR6 protects from inflammation and fibrosis in NEMO mice.

07:00 EST 23rd November 2018 | BioPortfolio

Summary of "CXCR6 protects from inflammation and fibrosis in NEMO mice."

Chronic inflammation in the liver provokes fibrosis and, on long-term, carcinogenesis. This sequence is prototypically recapitulated in mice with hepatocyte-specific knock-out of the NF-κB essential modulator (NEMO), termed NEMO mice, in which increased hepatocyte apoptosis and compensatory regeneration cause steatosis, inflammation and fibrosis. Natural killer T (NKT) cells carrying the chemokine receptor CXCR6 participate in liver inflammation and injury responses. Here, we investigated the role of CXCR6 in the NEMO mouse model. Unexpectedly, genetic deletion of CXCR6 enhanced hepatocyte death, inflammation and fibrosis in NEMO mice. Although CXCR6 expression is restricted to immune cells in the liver, the adoptive transfer of CXCR6 cells did not protect NEMOCxcr6 mice from hepatic injury. Gene array analyses revealed up-regulated stress response and metabolism pathways in hepatocytes from NEMOCxcr6 mice, functionally corresponding to an increased susceptibility of these hepatocytes to TNFα-induced cell death in vitro. These data revealed a novel CXCR6-dependent mechanism of suppressing inflammatory hepatocytic responses to cellular stress.


Journal Details

This article was published in the following journal.

Name: Biochimica et biophysica acta. Molecular basis of disease
ISSN: 1879-260X


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