1. Human monocyte-derived dendritic cells turn into foamy dendritic cells with IL-17A
- Author
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Fabienne Proamer, Karène Mahtouk, Emmanuelle Meugnier, Maurizio Aricò, Christine Delprat, Cyrille Debard, Daniel Hanau, Nathalie Bernoud-Hubac, Nathalie Bissay, Giulia Salvatore, Patricia Daira, Hubert Vidal, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), (France) CNRS, INSERM, Universite de Lyon 1, Institut Universitaire de France, Fondation pour l'Innovation et la Valorisation en Infectiologie, ANR Microbiologie-Immunologie-Environnement, LyonBiopole, Etablissement Francais du Sang EFS-Alsace, ARMESA (Association de Recherche et de Developpement en Medecine et Sante Publique), (Italy) Associazione Italiana Ricerca Istiocitosi (AIRI), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Analyses de Biologie Médicale (LABM), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS Alsace, Biologie des Cellules Dendritiques Humaines, EFS-Cancéropôle du Grand Est-Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Onco-Hematology, A.Meyer Children's Hospital, Université de Lyon, Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Delprat, Christine, and Mahtouk, Karène
- Subjects
Macrophages/immunology/metabolism ,Cellular differentiation ,[SDV]Life Sciences [q-bio] ,immunology ,monocytes ,inflammation ,microarrays ,lipidomics ,interleukin 17A ,lipid ,immunometabolism ,Cell Differentiation/genetics ,Lipid Droplets/immunology/metabolism ,Inflammation ,Foam Cells/metabolism ,Biology ,Biochemistry ,Interleukin-17/genetics/immunology/*metabolism ,Proinflammatory cytokine ,chemistry.chemical_compound ,Cell Proliferation/genetics ,Endocrinology ,Lipid droplet ,medicine ,Oil Red O ,Humans ,T-Lymphocytes/immunology/metabolism ,cytokine proinflammatoire ,pathogénèse ,Liver X receptor ,maladie inflammatoire ,ComputingMilieux_MISCELLANEOUS ,Monocytes/immunology/metabolism ,Atherosclerosis/immunology/*metabolism/pathology ,Fatty Acids/*metabolism ,Lipid metabolism ,Cell Biology ,Dendritic Cells/immunology/*metabolism ,3. Good health ,Cell biology ,chemistry ,Gene Expression Regulation ,Immunology ,Orphan Nuclear Receptors/biosynthesis/metabolism ,lipids (amino acids, peptides, and proteins) ,Interleukin 17 ,medicine.symptom ,Lipid Metabolism/immunology - Abstract
International audience; 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-alpha, 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.
- Published
- 2015
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