CD1d-mediated presentation of endogenous lipid antigens by adipocytes requires microsomal triglyceride transfer protein (MTP)

Maryam Rakhshandehroo, Sanne M W Gijzel, Rasmus Siersbæk, Marjoleine F Broekema, Colin de Haar, Henk S Schipper, Marianne Boes, Susanne Mandrup, Eric Kalkhoven

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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 upregulated 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/CD1d complexes by 3T3-L1 adipocytes. Furthermore, we identified microsomal triglyceride transfer protein (MTP), 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 (APCs), which may present an important aspect of adipocyte-immune cell communication in the regulation of whole body energy metabolism and immune homeostasis.

OriginalsprogEngelsk
TidsskriftJournal of Biological Chemistry
Vol/bind289
Sider (fra-til)22128-22139
ISSN0021-9258
DOI
StatusUdgivet - 25. jun. 2014

Fingeraftryk

Adipocytes
Lipids
Antigens
CCAAT-Enhancer-Binding Proteins
Adipose Tissue
Machinery
CD1d Antigen
Tissue homeostasis
Homeostasis
Saposins
Galactosidases
Tissue
Adipogenesis
T-cells
Lymphocytes
Antigen Presentation
Medical problems
microsomal triglyceride transfer protein
Cell Communication
Type 2 Diabetes Mellitus

Citer dette

Rakhshandehroo, Maryam ; Gijzel, Sanne M W ; Siersbæk, Rasmus ; Broekema, Marjoleine F ; de Haar, Colin ; Schipper, Henk S ; Boes, Marianne ; Mandrup, Susanne ; Kalkhoven, Eric. / CD1d-mediated presentation of endogenous lipid antigens by adipocytes requires microsomal triglyceride transfer protein (MTP). I: Journal of Biological Chemistry. 2014 ; Bind 289. s. 22128-22139.
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title = "CD1d-mediated presentation of endogenous lipid antigens by adipocytes requires microsomal triglyceride transfer protein (MTP)",
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 upregulated 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/CD1d complexes by 3T3-L1 adipocytes. Furthermore, we identified microsomal triglyceride transfer protein (MTP), 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 (APCs), which may present an important aspect of adipocyte-immune cell communication in the regulation of whole body energy metabolism and immune homeostasis.",
author = "Maryam Rakhshandehroo and Gijzel, {Sanne M W} and Rasmus Siersb{\ae}k and Broekema, {Marjoleine F} and {de Haar}, Colin and Schipper, {Henk S} and Marianne Boes and Susanne Mandrup and Eric Kalkhoven",
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doi = "10.1074/jbc.M114.551242",
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CD1d-mediated presentation of endogenous lipid antigens by adipocytes requires microsomal triglyceride transfer protein (MTP). / Rakhshandehroo, Maryam; Gijzel, Sanne M W; Siersbæk, Rasmus; Broekema, Marjoleine F; de Haar, Colin; Schipper, Henk S; Boes, Marianne; Mandrup, Susanne; Kalkhoven, Eric.

I: Journal of Biological Chemistry, Bind 289, 25.06.2014, s. 22128-22139.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - CD1d-mediated presentation of endogenous lipid antigens by adipocytes requires microsomal triglyceride transfer protein (MTP)

AU - Rakhshandehroo, Maryam

AU - Gijzel, Sanne M W

AU - Siersbæk, Rasmus

AU - Broekema, Marjoleine F

AU - de Haar, Colin

AU - Schipper, Henk S

AU - Boes, Marianne

AU - Mandrup, Susanne

AU - Kalkhoven, Eric

N1 - Copyright © 2014, The American Society for Biochemistry and Molecular Biology.

PY - 2014/6/25

Y1 - 2014/6/25

N2 - 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 upregulated 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/CD1d complexes by 3T3-L1 adipocytes. Furthermore, we identified microsomal triglyceride transfer protein (MTP), 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 (APCs), which may present an important aspect of adipocyte-immune cell communication in the regulation of whole body energy metabolism and immune homeostasis.

AB - 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 upregulated 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/CD1d complexes by 3T3-L1 adipocytes. Furthermore, we identified microsomal triglyceride transfer protein (MTP), 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 (APCs), which may present an important aspect of adipocyte-immune cell communication in the regulation of whole body energy metabolism and immune homeostasis.

U2 - 10.1074/jbc.M114.551242

DO - 10.1074/jbc.M114.551242

M3 - Journal article

VL - 289

SP - 22128

EP - 22139

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

ER -