Human monocyte-derived dendritic cells turn into foamy dendritic cells with IL-17A

J Lipid Res. 2015 Jun;56(6):1110-22. doi: 10.1194/jlr.M054874. Epub 2015 Apr 1.

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.

Keywords: immunology; immunometabolism; inflammation; interleukin 17A; lipid; lipidomics; microarrays; monocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atherosclerosis / immunology
  • Atherosclerosis / metabolism*
  • Atherosclerosis / pathology
  • Cell Differentiation / genetics
  • Cell Proliferation / genetics
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Fatty Acids / metabolism*
  • Foam Cells / metabolism
  • Gene Expression Regulation
  • Humans
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism*
  • Lipid Droplets / immunology
  • Lipid Droplets / metabolism
  • Lipid Metabolism / immunology
  • Liver X Receptors
  • Macrophages / immunology
  • Macrophages / metabolism
  • Monocytes / immunology
  • Monocytes / metabolism
  • Orphan Nuclear Receptors / biosynthesis
  • Orphan Nuclear Receptors / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Fatty Acids
  • IL17A protein, human
  • Interleukin-17
  • Liver X Receptors
  • NR1H3 protein, human
  • Orphan Nuclear Receptors

Associated data

  • GEO/GSE53163