| First Author | Liepelt A | Year | 2019 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1865 |
| Issue | 2 | Pages | 391-402 |
| PubMed ID | 30476545 | Mgi Jnum | J:270187 |
| Mgi Id | MGI:6277328 | Doi | 10.1016/j.bbadis.2018.11.020 |
| Citation | Liepelt A, et al. (2019) CXCR6 protects from inflammation and fibrosis in NEMO(LPC-KO) mice. Biochim Biophys Acta Mol Basis Dis 1865(2):391-402 |
| abstractText | 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-kappaB essential modulator (NEMO), termed NEMO(LPC-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 NEMO(LPC-KO) mouse model. Unexpectedly, genetic deletion of CXCR6 enhanced hepatocyte death, inflammation and fibrosis in NEMO(LPC-KO) mice. Although CXCR6 expression is restricted to immune cells in the liver, the adoptive transfer of CXCR6(+) cells did not protect NEMO(LPC-KO)Cxcr6(-/-) mice from hepatic injury. Gene array analyses revealed up-regulated stress response and metabolism pathways in hepatocytes from NEMO(LPC-KO)Cxcr6(-/-) mice, functionally corresponding to an increased susceptibility of these hepatocytes to TNFalpha-induced cell death in vitro. These data revealed a novel CXCR6-dependent mechanism of suppressing inflammatory hepatocytic responses to cellular stress. |
