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  • Review Article
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Invariant natural killer T cells in rheumatic disease: a joint dilemma

Nature Reviews Rheumatology volume 6, pages 90–98 (2010)Cite this article

Subjects

Abstract

Invariant natural killer T (iNKT) cells are an innate T-cell lineage known to recognize a range of endogenously derived and exogenously derived glycolipid antigens. Advances in our understanding of this T-cell subset have enabled researchers to investigate the immunomodulatory activity of iNKT cell ligands in experimental models of diseases such as cancer, allergy and chronic inflammatory joint disease. To a large extent, the ability of iNKT cells to regulate such disease models has been ascribed to their capacity to promote a polarized cytokine environment, which is understood to skew adaptive immune responses. In this Review, we discuss the current understanding of how iNKT-cell polarization is regulated and relate this basic theory to the proposed role for iNKT cells in models of rheumatologic disease.

Key Points

  • Invariant natural killer T (iNKT) cells are positively selected in the thymus by CD1d-expressing T-cell precursors

  • iNKT cells in mice and humans constitute a heterogeneous population of cells capable of producing a broad spectrum of cytokines

  • Cytokine production by iNKT cells is regulated by both antigen-dependent and antigen-independent mechanisms; these modes of activation are not necessarily mutually exclusive

  • iNKT cell activation in rheumatic disease might be dependent on the presence of glycolipid antigens of host origin as well as exogenously derived antigens

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Figure 1: Development of iNKT cells in mice.
Figure 2: Models of iNKT cell activation in response to exogenous antigens.
Figure 3: Models of iNKT cell activation in response to endogenous antigens.

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  1. Department of Rheumatology, Laboratory for Molecular Immunology and Inflammation, Ghent University Hospital, 185 De Pintelaan, Ghent, B-9000, Belgium

    Michael B. Drennan, Sandrine Aspeslagh & Dirk Elewaut

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  1. Michael B. Drennan
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  2. Sandrine Aspeslagh
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  3. Dirk Elewaut
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Correspondence to Dirk Elewaut.

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Drennan, M., Aspeslagh, S. & Elewaut, D. Invariant natural killer T cells in rheumatic disease: a joint dilemma. Nat Rev Rheumatol 6, 90–98 (2010). https://doi.org/10.1038/nrrheum.2009.261

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