CXCR6 deficiency ameliorates ischemia-reperfusion injury by reducing the recruitment and cytokine production of hepatic NKT cells in a mouse model of non-alcoholic fatty liver disease.

Authors:
Dr. Qi Zhang, PhD
Dr. Qi Zhang, PhD
Shandong University
Jinan, Shandong | China
Guihua Chen
Guihua Chen
The Third Affiliated Hospital of Sun Yat-sen University
China

Int Immunopharmacol 2019 Apr 16;72:224-234. Epub 2019 Apr 16.

Department of Hepatic Surgery and Liver Transplantation Center of The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China. Electronic address:

Fatty liver is used for transplantation due to organ shortage, but prone to cause complications like ischemia-reperfusion injury (IRI). NKT cells as a bridge between innate and adaptive immunity were reported to infiltrate the liver at the early phase of IRI induced in normal liver. However, the localization mechanism of NKT cells is not precise, and the role of NKT cells in fatty liver IRI is poorly understood. In present murine IRI model of non-alcoholic fatty liver disease, we demonstrated that although the number reduced in fatty liver, NKT cells still activated and accumulated to fatty liver following IRI, and contributed to IRI by producing inflammatory cytokine IFN-γ. We revealed that NKT cells in fatty liver expressed more CXCR6, a vital chemokine receptor; meanwhile, the ligand CXCL16 mRNA expression level in fatty liver was up-regulated. The up-regulation of the CXCR6/CXCL16 axis in fatty liver happened in IRI, which maybe endow NKT cells more chemotaxis. We further found CXCR6 deficiency reduced the recruitment of NKT cells in a tissue-dependent manner, and impaired the IFN-γ producing capacity of hepatic NKT cells. Serum ALT level and hepatic histology were both improved in CXCR6 deficient mice. The results provide evidence of the pathogenic role of NKT cells in fatty liver IRI, and important localization mechanism involving up-regulated CXCR6/CXCL16. Deficiency of CXCR6 protects the fatty liver from IRI by reducing the recruitment and cytokine production of hepatic NKT cells.

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http://dx.doi.org/10.1016/j.intimp.2019.04.021DOI Listing
April 2019
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