CD1d-mediated Presentation of Endogenous Lipid Antigens by Adipocytes Requires Microsomal Triglyceride Transfer Protein

• Published in: The Journal of biological chemistry Vol. 289; no. 32; pp. 22128 - 22139
• Main Authors: Rakhshandehroo, Maryam, Gijzel, Sanne M.W., Siersbæk, Rasmus, Broekema, Marjoleine F., de Haar, Colin, Schipper, Henk S., Boes, Marianne, Mandrup, Susanne, Kalkhoven, Eric
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.08.2014; American Society for Biochemistry and Molecular Biology
• Subjects: 3T3-L1 Cells; Adipocytes - immunology; Adipocytes - metabolism; Adipogenesis - genetics; Adipogenesis - immunology; Animals; Antigen Presentation; Antigens, CD1d - genetics; Antigens, CD1d - metabolism; Carrier Proteins - genetics; Carrier Proteins - metabolism; CCAAT-Enhancer-Binding Protein-beta - genetics; CCAAT-Enhancer-Binding Protein-beta - metabolism; CCAAT-Enhancer-Binding Protein-delta - genetics; CCAAT-Enhancer-Binding Protein-delta - metabolism; Cell Communication - immunology; Energy Metabolism; Gene Expression; Gene Knockdown Techniques; Gene Regulation; Humans; Lipids - immunology; Mice; Natural Killer T-Cells - immunology; Transcription, Genetic; Adipocyte; Adipose Tissue Metabolism; CCAAT-Enhancer-binding Protein (C/EBP); Antigen Presentation; Lipid
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M114.551242

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.