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  • Review Article
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Natural killer T cells in atherosclerosis

Nature Reviews Cardiology volume 14, pages 304–314 (2017)Cite this article

Subjects

Key Points

  • Natural killer T (NKT) cells are activated by the interaction of CD1d molecules containing antigenic exogenous lipids or endogenous self-lipids on antigen-presenting cells, with the semi-invariant T cell receptor on NKT cells

  • Antigenic lipids include glycolipids and phospholipids of microbial origin or self-lipids

  • NKT cells can also be activated in a CD1d-independent manner by Toll-like receptor stimulation of IL-18 and IL-22 secretion

  • Activation of NKT cells results in the rapid release of TH1, TH2, and TH17 cytokines and the cytotoxic proteins perforin and granzyme B

  • Numerous murine studies have shown that NKT cells are proatherogenic; NKT cells can promote atherosclerosis by activation of their secreted cytokines on immune cells present in the atherosclerotic lesion and by the induction of apoptosis by cytotoxic proteins

Abstract

Atherosclerosis is a chronic inflammatory disorder that develops in response to hyperlipidaemia. Cells from both the innate and adaptive immune systems contribute to the development of atherosclerotic lesions. The role of natural killer T (NKT) cells in response to microbial pathogens and inflammatory disorders such as atherosclerosis has received increasing attention in the past 10–15 years. Endogenous self-lipid antigens and exogenous lipid antigens, including those on microorganisms can activate NKT cells. CD1d molecules on antigen-presenting cells present these lipids to the T-cell receptor on NKT cells, which results in the rapid production of cytokines and cytotoxic proteins. NKT cells can also be activated in a CD1d-independent manner. Numerous studies have shown that NKT cells can promote atherogenesis. Various NKT cell sublineages have been described, but the participation of each in atherogenesis requires further characterization. In this Review, we provide an overview of NKT cells in the immune system, discuss CD1 molecules and lipid antigen presentation, and describe the interaction of the CD1d–NKT cell network with gut microbiota and its effect in modulating the activity or levels of NKT cells, which might in turn influence atherosclerosis. Although the exact mechanisms by which NKT cells promote atherosclerosis have not been fully elucidated, several potential mechanisms are proposed.

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Figure 1: Invariant natural killer T (iNKT) cell sublineages.
Figure 2: Invariant natural killer T (iNKT) cells promote atherogenesis.
Figure 3: Gut microbiome and natural killer T (NKT) cells.

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Acknowledgements

This work is supported by National Institutes of Health grant HL088420.

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Authors and Affiliations

  1. Department of Pathology, University of Chicago, 5841 South Maryland Avenue, Chicago, 60637, Illinois, USA

    Godfrey S. Getz

  2. Ben May Institute for Cancer Biology, 929 East 57th Street, University of Chicago, Chicago, 60637, Illinois, USA

    Catherine A. Reardon

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Getz, G., Reardon, C. Natural killer T cells in atherosclerosis. Nat Rev Cardiol 14, 304–314 (2017). https://doi.org/10.1038/nrcardio.2017.2

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