CXCR6 protects from inflammation and fibrosis in NEMOLPC-KO mice

Anke Liepelt, Alexander Wehr, Marlene Kohlhepp, Jana C. Mossanen, Karina Kreggenwinkel, Bernd Denecke, Ivan G. Costa, Tom Luedde, Christian Trautwein, Frank Tacke

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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 NEMOLPC-KO 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 NEMOLPC-KO mouse model. Unexpectedly, genetic deletion of CXCR6 enhanced hepatocyte death, inflammation and fibrosis in NEMOLPC-KO mice. Although CXCR6 expression is restricted to immune cells in the liver, the adoptive transfer of CXCR6+ cells did not protect NEMOLPC-KOCxcr6−/− mice from hepatic injury. Gene array analyses revealed up-regulated stress response and metabolism pathways in hepatocytes from NEMOLPC-KOCxcr6−/− 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.

Original languageEnglish
Pages (from-to)391-402
Number of pages12
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Issue number2
StatePublished - 1 Feb 2019
Externally publishedYes


  • Chemokine receptor
  • Hepatocytes
  • Inflammation
  • Liver fibrosis


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