Interleukin-15-mediated inflammation promotes non-alcoholic fatty liver disease. (June 2016)

• Record Type: Journal Article
• Authors: Cepero-Donates, Yuneivy; Lacraz, Grégory; Ghobadi, Farnaz; Rakotoarivelo, Volatiana; Orkhis, Sakina; Mayhue, Marian; Chen, Yi-Guang; Rola-Pleszczynski, Marek; Menendez, Alfredo; Ilangumaran, Subburaj; Ramanathan, Sheela
• Is Part Of: Cytokine. Volume 82(2016)
• Page Start: 102
• Page End: 111
• Publication Date: 2016-06
• Subjects: NAFLD non-alcoholic fatty liver disease -- IHL intrahepatic lymphocytes -- NASH non-alcoholic steatohepatitis -- PPAR peroxisome proliferator-activated receptor -- ER endoplasmic reticulum; Interleukin-15 -- NAFLD -- Mice -- Liver -- Inflammation; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2016.01.020
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: Absence of IL-15 or IL-15Rα protects from NAFLD. Production of chemokines is decreased in the absence of IL-15 or IL-15Rα. In NAFLD, CD4 +, CD8 +, NK and NKT cells are increased in numbers in the liver. Abstract: Interleukin-15 (IL-15) is essential for the homeostasis of lymphoid cells particularly memory CD8 + T cells and NK cells. These cells are abundant in the liver, and are implicated in obesity-associated pathogenic processes. Here we characterized obesity-associated metabolic and cellular changes in the liver of mice lacking IL-15 or IL-15Rα. High fat diet-induced accumulation of lipids was diminished in the livers of mice deficient for IL-15 or IL-15Rα. Expression of enzymes involved in the transport of lipids in the liver showed modest differences. More strikingly, the liver tissues of IL15-KO and IL15Rα-KO mice showed decreased expression of chemokines CCl2, CCL5 and CXCL10 and reduced infiltration of mononuclear cells. In vitro, IL-15 stimulation induced chemokine gene expression in wildtype hepatocytes, but not in IL15Rα-deficient hepatocytes. Our results show that IL-15 is implicated in the high fat diet-induced lipid accumulation and inflammation in the liver, leading to fatty liver disease.