title: CD1d-mediated presentation of endogenous lipid antigens by adipocytes requires microsomal triglyceride transfer protein.
abstract: Obesity-induced adipose tissue (AT) dysfunction results in a chronic low-grade inflammation that predisposes to the development of insulin resistance and type 2 diabetes. During the development of obesity, the AT-resident immune cell profile alters to create a pro-inflammatory state. Very recently, CD1d-restricted invariant (i) natural killer T (NKT) cells, a unique subset of lymphocytes that are reactive to so called lipid antigens, were implicated in AT homeostasis. Interestingly, recent data also suggest that human and mouse adipocytes can present such lipid antigens to iNKT cells in a CD1d-dependent fashion, but little is known about the lipid antigen presentation machinery in adipocytes. Here we show that CD1d, as well as the lipid antigen loading machinery genes pro-saposin (Psap), Niemann Pick type C2 (Npc2), α-galactosidase (Gla), are up-regulated in early adipogenesis, and are transcriptionally controlled by CCAAT/enhancer-binding protein (C/EBP)-β and -δ. Moreover, adipocyte-induced Th1 and Th2 cytokine release by iNKT cells also occurred in the absence of exogenous ligands, suggesting the display of endogenous lipid antigen-D1d complexes by 3T3-L1 adipocytes. Furthermore, we identified microsomal triglyceride transfer protein, which we show is also under the transcriptional regulation of C/EBPβ and -δ, as a novel player in the presentation of endogenous lipid antigens by adipocytes. Overall, our findings indicate that adipocytes can function as non-professional lipid antigen presenting cells, which may present an important aspect of adipocyte-immune cell communication in the regulation of whole body energy metabolism and immune homeostasis.
authors: From the Molecular Cancer Research, Center for Molecular Medicine and.
authors: Maryam
authors: M
authors: Rakhshandehroo
authors: From the Molecular Cancer Research, Center for Molecular Medicine and.
authors: Sanne M W
authors: SM
authors: Gijzel
authors: the Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark.
authors: Rasmus
authors: R
authors: Siersbæk
authors: From the Molecular Cancer Research, Center for Molecular Medicine and.
authors: Marjoleine F
authors: MF
authors: Broekema
authors: the Department of Pediatric Immunology, University Medical Center Utrecht, 3584 CG Utrecht, the Netherlands and.
authors: Colin
authors: C
authors: de Haar
authors: From the Molecular Cancer Research, Center for Molecular Medicine and the Department of Pediatric Immunology, University Medical Center Utrecht, 3584 CG Utrecht, the Netherlands and.
authors: Henk S
authors: HS
authors: Schipper
authors: the Department of Pediatric Immunology, University Medical Center Utrecht, 3584 CG Utrecht, the Netherlands and.
authors: Marianne
authors: M
authors: Boes
authors: the Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark.
authors: Susanne
authors: S
authors: Mandrup
authors: From the Molecular Cancer Research, Center for Molecular Medicine and e.kalkhoven@umcutrecht.nl.
authors: Eric
authors: E
authors: Kalkhoven
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000276:immunology* / Q000378:metabolism*; D050156:Adipogenesis / Q000235:genetics / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation; D055610:Antigens, CD1d / Q000235:genetics / Q000378:metabolism*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002450:Cell Communication / Q000276:immunology; D004734:Energy Metabolism; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D008055:Lipids / Q000276:immunology*; D051379:Mice; D055611:Natural Killer T-Cells / Q000276:immunology; D014158:Transcription, Genetic
chemical_list: D055610:Antigens, CD1d; D022782:CCAAT-Enhancer-Binding Protein-beta; D002352:Carrier Proteins; C545013:Cebpb protein, mouse; C497253:Cebpd protein, mouse; D008055:Lipids; C106092:microsomal triglyceride transfer protein; D051743:CCAAT-Enhancer-Binding Protein-delta
keywords: Adipocyte; Adipose Tissue Metabolism; Antigen Presentation; CCAAT-Enhancer-binding Protein (C/EBP); Lipid