IL-10–producing NKT10 cells are a distinct regulatory invariant NKT cell subset
Duygu Sag, … , Mitchell Kronenberg, Gerhard Wingender
Duygu Sag, … , Mitchell Kronenberg, Gerhard Wingender
Published July 25, 2014
Citation Information: J Clin Invest. 2014;124(9):3725-3740. https://doi.org/10.1172/JCI72308.
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Research Article Immunology

IL-10–producing NKT10 cells are a distinct regulatory invariant NKT cell subset

Abstract

Invariant natural killer T (iNKT) cells rapidly produce copious amounts of multiple cytokines after activation, thereby impacting a wide variety of different immune reactions. However, strong activation of iNKT cells with α-galactosylceramide (αGalCer) reportedly induces a hyporeactive state that resembles anergy. In contrast, we determined here that iNKT cells from mice pretreated with αGalCer retain cytotoxic activity and maintain the ability to respond to TCR-dependent as well as TCR-independent cytokine-mediated stimulation. Additionally, αGalCer-pretreated iNKT cells acquired characteristics of regulatory cells, including production and secretion of the immunomodulatory cytokine IL-10. Through the production of IL-10, αGalCer-pretreated iNKT cells impaired antitumor responses and reduced disease in experimental autoimmune encephalomyelitis, a mouse model of autoimmune disease. Furthermore, a subset of iNKT cells with a similar inhibitory phenotype and function were present in mice not exposed to αGalCer and were enriched in mouse adipose tissue and detectable in human PBMCs. These data demonstrate that IL-10–producing iNKT cells with regulatory potential (NKT10 cells) represent a distinct iNKT cell subset.

Authors

Duygu Sag, Petra Krause, Catherine C. Hedrick, Mitchell Kronenberg, Gerhard Wingender

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Figure 10

NKT10 cells are enriched in WAT.

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NKT10 cells are enriched in WAT. (A and B) Il10GFP mice were left untrea...
(A and B) Il10GFP mice were left untreated or were i.v. injected with 1 μg αGalCer, and iNKT cells in spleen and scWAT were analyzed 16 hours later. (A) Expression of EGFP and CD49d from 1 representative experiment. Numbers in the dot plots denote the percentage of cells in the respective quadrants. (B) Percentage of EGFP+ (light gray) and EGFP– (dark gray) iNKT cells from spleen and scWAT was calculated as the percentage of iNKT cells in untreated control mice. P < 0.001 for spleen versus scWAT for all comparisons. Graph summarizes data from 4 independent experiments with 13 mice per group. (C and D) iNKT cells from spleen and scWAT of C57BL/6 mice were analyzed for expression of the indicated markers. Representative data (C) and a summary graph (D) are shown. Numbers in the histograms in C denote the geometric mean values for the depicted antigens on iNKT cells. Representative data from 1 of at least 3 independent experiments are shown.