title: Human monocyte-derived dendritic cells turn into foamy dendritic cells with IL-17A.
abstract: Interleukin 17A (IL-17A) is a proinflammatory cytokine involved in the pathogenesis of chronic inflammatory diseases. In the field of immunometabolism, we have studied the impact of IL-17A on the lipid metabolism of human in vitro-generated monocyte-derived dendritic cells (DCs). Microarrays and lipidomic analysis revealed an intense remodeling of lipid metabolism induced by IL-17A in DCs. IL-17A increased 2-12 times the amounts of phospholipids, cholesterol, triglycerides, and cholesteryl esters in DCs. Palmitic (16:0), stearic (18:0), and oleic (18:ln-9c) acid were the main fatty acid chains present in DCs. They were strongly increased in response to IL-17A while their relative proportion remained unchanged. Capture of extracellular lipids was the major mechanism of lipid droplet accumulation, visualized by electron microscopy and Oil Red O staining. Besides this foamy phenotype, IL-17A induced a mixed macrophage-DC phenotype and expression of the nuclear receptor NR1H3/liver X receptor-α, previously identified in the context of atherosclerosis as the master regulator of cholesterol homeostasis in macrophages. These IL-17A-treated DCs were as competent as untreated DCs to stimulate allogeneic naive T-cell proliferation. Following this first characterization of lipid-rich DCs, we propose to call these IL-17A-dependent cells "foamy DCs" and discuss the possible existence of foamy DCs in atherosclerosis, a metabolic and inflammatory disorder involving IL-17A.
authors.affiliation: CNRS, UMR5239, Laboratoire de Biologie Moléculaire de la Cellule, 69007 Lyon, France Ecole Normale Supérieure de Lyon, 69007 Lyon, France Université de Lyon, 69003 Lyon, France Université de Lyon 1, 69622 Villeurbanne, France Université de Florence, 50134 Florence, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Salvatore
authors.affiliation: INSERM, U 1060 (CarMeN), INRA U1235, Institut Multidisciplinaire de Biochimie des Lipides, Institut National des Sciences Appliqués, 69621 Villeurbanne, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bernoud-Hubac
authors.affiliation: CNRS, UMR5239, Laboratoire de Biologie Moléculaire de la Cellule, 69007 Lyon, France Ecole Normale Supérieure de Lyon, 69007 Lyon, France Université de Lyon, 69003 Lyon, France Université de Lyon 1, 69622 Villeurbanne, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bissay
authors.affiliation: INSERM, U 1060 (CarMeN), INRA U1235, Institut Multidisciplinaire de Biochimie des Lipides, Institut National des Sciences Appliqués, 69621 Villeurbanne, France.
authors.forename: Cyrille
authors.initials: C
authors.lastname: Debard
authors.affiliation: Functional Lipidomics Platform, Institut Multidisciplinaire de Biochimie des Lipides/Carnot Lisa, INSA-Lyon, 69622 Villeurbanne, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Daira
authors.affiliation: INSERM, U 1060 (CarMeN), INRA U1235, Institut Multidisciplinaire de Biochimie des Lipides, Institut National des Sciences Appliqués, 69621 Villeurbanne, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Meugnier
authors.affiliation: Unité Mixte de Recherche Santé UMR S949, Institut National de la Santé et de la Recherche Médicale, 67000 Strasbourg, France Université de Strasbourg, 67400 Strasbourg, France Histocompatibility Laboratory, Etablissement Français du Sang-Alsace, 67000 Strasbourg, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Proamer
authors.affiliation: Unité Mixte de Recherche Santé UMR S949, Institut National de la Santé et de la Recherche Médicale, 67000 Strasbourg, France Université de Strasbourg, 67400 Strasbourg, France Histocompatibility Laboratory, Etablissement Français du Sang-Alsace, 67000 Strasbourg, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hanau
authors.affiliation: INSERM, U 1060 (CarMeN), INRA U1235, Institut Multidisciplinaire de Biochimie des Lipides, Institut National des Sciences Appliqués, 69621 Villeurbanne, France.
authors.forename: Hubert
authors.initials: H
authors.lastname: Vidal
authors.affiliation: Istituto Toscano Tumori (I.T.T), 50139 Florence, Italy Azienda Sanitaria Provinciale 7, 97100 Ragusa, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Aricò
authors.affiliation: CNRS, UMR5239, Laboratoire de Biologie Moléculaire de la Cellule, 69007 Lyon, France Ecole Normale Supérieure de Lyon, 69007 Lyon, France Université de Lyon, 69003 Lyon, France Université de Lyon 1, 69622 Villeurbanne, France Institut Universitaire de France, 75005 Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Delprat
authors.affiliation: CNRS, UMR5239, Laboratoire de Biologie Moléculaire de la Cellule, 69007 Lyon, France Ecole Normale Supérieure de Lyon, 69007 Lyon, France Université de Lyon, 69003 Lyon, France Université de Lyon 1, 69622 Villeurbanne, France.
authors.forename: Karène
authors.initials: K
authors.lastname: Mahtouk
mesh_terms: D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005487:Foam Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D066292:Lipid Droplets / Q000276:immunology / Q000378:metabolism; D050356:Lipid Metabolism / Q000276:immunology; D000071518:Liver X Receptors; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000096:biosynthesis / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D005227:Fatty Acids; C508717:IL17A protein, human; D020381:Interleukin-17; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors
keywords: immunology; immunometabolism; inflammation; interleukin 17A; lipid; lipidomics; microarrays; monocytes
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