title: Interleukin-15-mediated inflammation promotes non-alcoholic fatty liver disease.
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.
authors: Division of Immunology, Departments of Pediatrics, Université de Sherbrooke, Sherbrooke, Québec, QC J1H 5N4, Canada.
authors: Yuneivy
authors: Y
authors: Cepero-Donates
authors: Division of Immunology, Departments of Pediatrics, Université de Sherbrooke, Sherbrooke, Québec, QC J1H 5N4, Canada; Hubrecht Institute, University Medical Center, Utrecht, The Netherlands.
authors: Grégory
authors: G
authors: Lacraz
authors: Division of Immunology, Departments of Pediatrics, Université de Sherbrooke, Sherbrooke, Québec, QC J1H 5N4, Canada.
authors: Farnaz
authors: F
authors: Ghobadi
authors: Division of Immunology, Departments of Pediatrics, Université de Sherbrooke, Sherbrooke, Québec, QC J1H 5N4, Canada.
authors: Volatiana
authors: V
authors: Rakotoarivelo
authors: Division of Immunology, Departments of Pediatrics, Université de Sherbrooke, Sherbrooke, Québec, QC J1H 5N4, Canada.
authors: Sakina
authors: S
authors: Orkhis
authors: Division of Immunology, Departments of Pediatrics, Université de Sherbrooke, Sherbrooke, Québec, QC J1H 5N4, Canada.
authors: Marian
authors: M
authors: Mayhue
authors: Department of Pediatrics, Max McGee National Research Center for Juvenile Diabetes, Medical College of Wisconsin, Milwaukee, USA.
authors: Yi-Guang
authors: YG
authors: Chen
authors: Division of Immunology, Departments of Pediatrics, Université de Sherbrooke, Sherbrooke, Québec, QC J1H 5N4, Canada; CRCHUS, Sherbrooke, Québec, QC J1H 5N4, Canada.
authors: Marek
authors: M
authors: Rola-Pleszczynski
authors: Department of Microbiology and Infectious Diseases, Université de Sherbrooke, Sherbrooke, Québec, QC J1H 5N4, Canada; CRCHUS, Sherbrooke, Québec, QC J1H 5N4, Canada.
authors: Alfredo
authors: A
authors: Menendez
authors: Division of Immunology, Departments of Pediatrics, Université de Sherbrooke, Sherbrooke, Québec, QC J1H 5N4, Canada; CRCHUS, Sherbrooke, Québec, QC J1H 5N4, Canada.
authors: Subburaj
authors: S
authors: Ilangumaran
authors: Division of Immunology, Departments of Pediatrics, Université de Sherbrooke, Sherbrooke, Québec, QC J1H 5N4, Canada; CRCHUS, Sherbrooke, Québec, QC J1H 5N4, Canada. Electronic address: Sheela.Ramanathan@Usherbrooke.ca.
authors: Sheela
authors: S
authors: Ramanathan
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018925:Chemokines / Q000235:genetics / Q000276:immunology; D004041:Dietary Fats / Q000009:adverse effects / Q000494:pharmacology; D022781:Hepatocytes / Q000276:immunology*; D007156:Immunologic Memory; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D053647:Receptors, Interleukin-15 / Q000276:immunology
chemical_list: D018925:Chemokines; D004041:Dietary Fats; C508025:Il15ra protein, mouse; D019409:Interleukin-15; D053647:Receptors, Interleukin-15
keywords: Inflammation; Interleukin-15; Liver; Mice; NAFLD