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Tissue-specific functions of invariant natural killer T cells

Nature Reviews Immunology volume 18, pages 559–574 (2018)Cite this article

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Abstract

Invariant natural killer T cells (iNKT cells) are an innate-like T cell subset that expresses an invariant T cell receptor (TCR) α-chain and recognizes lipids presented on CD1d. They secrete diverse cytokines and can influence many types of immune responses. Despite having highly similar TCR specificities, iNKT cells differentiate in the thymus into distinct subsets that are analogous to T helper 1 (TH1), TH2 and TH17 cell subsets. Additional iNKT cell subsets that may require peripheral activation have also been described, including one that produces IL-10. In general, iNKT cells are non-circulating, tissue-resident lymphocytes, but the prevalence of different iNKT cell subsets differs markedly between tissues. Here, we summarize the functions of iNKT cells in four tissues in which they are prevalent, namely, the liver, the lungs, adipose tissue and the intestine. Importantly, we explain how local iNKT cell responses at each site contribute to tissue homeostasis and protection from infection but can also contribute to tissue inflammation and damage.

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Fig. 1: Tissue distribution of iNKT cell subsets in mice.
Fig. 2: iNKT cells in the liver sinusoids.
Fig. 3: iNKT cells in the lung.

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Acknowledgements

The authors’ work is supported by US National Institutes of Health (NIH) grants AI 71922, AI 92763, AI 105215 and AI 137230. C.M.C. is suqpported by American Lung Association Senior Research Training Fellowship RT-412662. The authors thank their colleagues for many helpful discussions.

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Nature Reviews Immunology thanks P. Brennan, M. Brenner, A. Lehuen and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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    Catherine M. Crosby & Mitchell Kronenberg

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Glossary

α-Galactosyl ceramide

(αGalCer). A glycosphingolipid that is a specific and highly potent activator of invariant natural killer T cells.

Concanavalin A

(Con A). A mitogenic lectin that stimulates T cell proliferation and activation and has been shown to induce invariant natural killer T cell-activated liver damage.

Myeloid-derived suppressor cells

(MDSCs). A heterogeneous group of myeloid cells that exhibits strong immunosuppressive function.

Visceral adipose tissue

(VAT). Adipose tissue that is located around internal organs in the abdominal cavity. Excess visceral fat has been linked to insulin resistance and other obesity-related diseases.

White adipose tissue

(WAT). White and brown adipose tissues are the two types of adipose tissue found in mammals. WAT is the primary tissue for energy storage and it also serves roles in whole body thermal insulation and endocrine regulation of energy homeostasis.

Meta-inflammation

A metabolically driven, chronic, low-grade inflammation that is manifested by immune cells and adipocytes. This inflammation has been linked to obesity and insulin resistance.

Mucosal-associated invariant T cells

An innate-like T cell type with an invariant T cell receptor α (TCRα) chain that recognizes vitamin B metabolites presented on the MHC class I-like molecule MHC class I-related gene protein (MR1).

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Crosby, C.M., Kronenberg, M. Tissue-specific functions of invariant natural killer T cells. Nat Rev Immunol 18, 559–574 (2018). https://doi.org/10.1038/s41577-018-0034-2

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