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Are human iNKT cells keeping tabs on lipidome perturbations triggered by oxidative stress in the blood?

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Abstract

The central paradigm of conventional MHC-restricted T cells is that they respond specifically to foreign peptides, while displaying tolerance to self-antigens. In contrast, it is now becoming clear that a number of innate-like T cell subsets—CD1-restricted T cells, Vγ9Vδ2 T cells, and MAIT cells—may operate by different rules: rather than focusing on the recognition of specific foreign antigens, these T cells all appear to respond to alterations to lipid-related pathways. By monitoring perturbations to the “lipidome,” these T cells may be able to spring into action to deal with physiological situations that are of self as well as microbial origin. iNKT cells are a prime example of this type of lipidome-reactive T cell. As a result of their activation by self lyso-phospholipid species that are generated downstream of blood lipid oxidation, human iNKT cells in the vasculature may respond sensitively to a variety of oxidative stresses. Some of the cytokines produced by activated iNKT cells have angiogenic effects (e.g., GM-CSF, IL-8), whereas others (e.g., IFN-γ) are pro-inflammatory factors that can propagate vascular pathology by influencing the functions of macrophages and dendritic cells. Consistent with this, evidence is accumulating that iNKT cells contribute to atherosclerosis, which is one of the most common inflammatory pathologies, and one that is integrally related to characteristics of the lipidome.

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  1. Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53706, USA

    Laura Felley & Jenny E. Gumperz

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  1. Laura Felley
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  2. Jenny E. Gumperz
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Correspondence to Jenny E. Gumperz.

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This article is published in the Special Issue CD1, MR1, NKT, and MAIT: Evolution and Origins of Non-peptidic Antigen Recognition by T lymphocytes with Guest Editor Dr. Dirk Zajonc

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Felley, L., Gumperz, J.E. Are human iNKT cells keeping tabs on lipidome perturbations triggered by oxidative stress in the blood?. Immunogenetics 68, 611–622 (2016). https://doi.org/10.1007/s00251-016-0936-8

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  • DOI: https://doi.org/10.1007/s00251-016-0936-8

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