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

Rakhshandehroo, Maryam; Gijzel, Sanne M.W.; Siersbæk, Rasmus; Broekema, Marjoleine F.; Haar, Colin de; Bateman, Scott; Boes, Marianne; Mandrup, Susanne; Kalkhoven, Eric

doi:10.1074/jbc.m114.551242

Cited by 31 publications

(46 citation statements)

References 57 publications

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“…iNKT cells in WAT produce more IL-4 and IL-10 and less IFN-γ than do iNKT cells in the liver and spleen (Lynch et al, 2012), suggesting that iNKT cells in WAT are in an “alternative activation” state. Consistent with this, recent work has shown that mammals produce endogenous lipid antigens such as α-galactosylceramides (αGalCer) that promote production of type 2 cytokines by iNKT cells (Kain et al, 2014), and that adipocytes can present lipid antigens to iNKT cells via CD1d (Huh et al, 2013; Rakhshandehroo et al, 2014). iNKT cells are decreased in murine and human obesity, and surgical or dietary treatment of obesity restores iNKT cells in WAT (Lynch et al, 2012).…”

Section: Introductionmentioning

confidence: 77%

Immune Regulation of Metabolic Homeostasis in Health and Disease

Brestoff

Artis

2015

Cell

404

356

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Obesity is an increasingly prevalent disease worldwide. While genetic and environmental factors are known to regulate the development of obesity and associated metabolic diseases, emerging studies indicate that innate and adaptive immune cell responses in adipose tissue have critical roles in the regulation of metabolic homeostasis. In the lean state, type 2 cytokine-associated immune cell responses predominate in white adipose tissue and protect against weight gain and insulin resistance through direct effects on adipocytes and elicitation of beige adipose. In obesity, these metabolically beneficial immunologic pathways become dysregulated, and adipocytes and other factors initiate metabolically deleterious type 1 inflammation that impairs glucose metabolism. This review discusses our current understanding of the functions of different types of adipose tissue, how immune cells regulate adipocyte function and metabolic homeostasis in the context of health and disease, and highlights the potential of targeting immuno-metabolic pathways as a therapeutic strategy to treat obesity and associated diseases.

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Section: Introductionmentioning

confidence: 77%

Immune Regulation of Metabolic Homeostasis in Health and Disease

Brestoff

Artis

2015

Cell

404

356

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“…Once activated, iNKT cells function as immune orchestrators by participating in bidirectional activation with antigen presenting cells and by transactivation of other effector leukocytes. Here, we have highlighted examples of crosstalk with Kupffer cells (Lee et al 2010), DCs (Arora et al 2014; Bai et al 2012; Brigl et al 2003; Cohen et al 2011; Tyznik et al 2008), MDSCs, CD8 + T cells (De Santo et al 2008), macrophage populations (Barral et al 2010; Kawakami et al 2003; Lee et al 2010; Nieuwenhuis et al 2002), and non-hematopoietic cells (Hua et al 2010; Huh et al 2013; Olszak et al 2014; Rakhshandehroo et al 2014; Satoh et al 2016; Zeissig et al 2012). In other examples that were not discussed here, iNKT cells have been shown to activate or modulate the function of granulocytes (De Santo et al 2010), B cells (Chang et al 2012; Galli et al 2007; King et al 2012; Leadbetter et al 2008), adaptive T cells (Fujii et al 2004; Hermans et al 2003), and NK cells (Carnaud et al 1999; Schmieg et al 2003).…”

Section: Discussionmentioning

confidence: 99%

“…Adipocytes express high levels of CD1d and have been reported to present antigenic lipids to adipose iNKT cells (Huh et al 2013; Rakhshandehroo et al 2014), a unique regulatory iNKT cell subset (Lynch et al 2015). CD1d is also expressed on the intestinal epithelium (Blumberg et al 1991; Olszak et al 2014).…”

Section: Lipid Uptake and Presentation By Cd1dmentioning

confidence: 99%

Activation strategies for invariant natural killer T cells

et al. 2016

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Invariant natural killer T (iNKT) cells are a specialized T cell subset that plays an important role in host defense, orchestrating both innate and adaptive immune effector responses against a variety of microbes. Specific microbial lipids and mammalian self lipids displayed by the antigen-presenting molecule CD1d can activate iNKT cells through their semi-invariant αβ T cell receptors (TCRs). iNKT cells also constitutively express receptors for inflammatory cytokines typically secreted by antigen-presenting cells (APCs) after recognition of pathogen-associated molecular patterns (PAMPs), and they can be activated through these cytokine receptors either in combination with TCR signals, or in some cases even in the absence of TCR signaling. During infection, experimental evidence suggests that both TCR-driven and cytokine-driven mechanisms contribute to iNKT cell activation. While the relative contributions of these two signaling mechanisms can vary widely depending on the infectious context, both lipid antigens and PAMPs mediate reciprocal activation of iNKT cells and APCs, leading to downstream activation of multiple other immune cell types to promote pathogen clearance. In this review, we discuss the mechanisms involved in iNKT cell activation during infection, focusing on the central contributions of both lipid antigens and PAMP-induced inflammatory cytokines, and highlight in vivo examples of activation during bacterial, viral, and fungal infections.

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“…In the human gut, intestinal epithelial cells express and present antigens by CD1d [5]. More recently, adipocytes were also found to express CD1d and a role in lipid antigen presentation has been suggested [6, 7]. CD1e is expressed on DCs but does not function as an antigen presenting molecule, since it is not present at the plasma membrane.…”

Section: Cd1 Moleculesmentioning

confidence: 99%

CD1-Restricted T Cells at the Crossroad of Innate and Adaptive Immunity

Pereira

Macedo

2016

Journal of Immunology Research

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Lipid-specific T cells comprise a group of T cells that recognize lipids bound to the MHC class I-like CD1 molecules. There are four isoforms of CD1 that are expressed at the surface of antigen presenting cells and therefore capable of presenting lipid antigens: CD1a, CD1b, CD1c, and CD1d. Each one of these isoforms has distinct structural features and cellular localizations, which promotes binding to a broad range of different types of lipids. Lipid antigens originate from either self-tissues or foreign sources, such as bacteria, fungus, or plants and their recognition by CD1-restricted T cells has important implications in infection but also in cancer and autoimmunity. In this review, we describe the characteristics of CD1 molecules and CD1-restricted lipid-specific T cells, highlighting the innate-like and adaptive-like features of different CD1-restricted T cell subtypes.

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

Cited by 31 publications

References 57 publications

Immune Regulation of Metabolic Homeostasis in Health and Disease

Immune Regulation of Metabolic Homeostasis in Health and Disease

Activation strategies for invariant natural killer T cells

CD1-Restricted T Cells at the Crossroad of Innate and Adaptive Immunity

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