Prostaglandin D2 inhibits the production of IFN-gamma by invariant NK T cells: consequences in the control of B16 melanoma

The Journal of Immunology : Official Journal of the American Association of Immunologists
David TorresFrançois Trottein

Abstract

Invariant NK T (iNKT) cells are a subset of innate/memory lymphocytes that recognize lipid Ags presented by CD1d-expressing APCs such as dendritic cells (DCs). Upon primary stimulation through their TCR, iNKT cells promptly produce large amounts of IFN-gamma and/or IL-4 that play critical roles in the regulation of innate and adaptive immune responses. To date, the role of environmental factors on iNKT cell functions has been poorly investigated. In this study, we addressed the question of whether PGD2, a potent eicosanoid lipid mediator involved in immune responses and inflammation, could be important in DC/iNKT cell cross-talk. We show that PGD2 dramatically reduced the production of IFN-gamma, but not IL-4, by iNKT cells in response to the superagonist alpha-galactosylceramide (alpha-GalCer) both in vitro and in vivo. This effect is mediated by the D prostanoid receptor 1 (DP1) expressed by DCs and iNKT cells and requires protein kinase A activation. We also report that PGD2 and BW245C (a selective DP1 agonist) reduce the protective effects of alpha-GalCer in B16F10-induced melanoma metastasis, an effect that depends on IFN-gamma production by iNKT cells. As a whole, these data reveal novel pathways regulating iNKT cell biol...Continue Reading

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Citations

Nov 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Woo-Sung ChangChang-Yuil Kang
Aug 27, 2011·Respiratory Research·Berislav BosnjakMichelle M Epstein
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Apr 27, 2020·Arthritis & Rheumatology·Mehdi NajarHassan Fahmi
Oct 7, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zeina JaffarKevan Roberts
Apr 23, 2020·Advances in Wound Care·Carlos Poblete JaraEliana Pereira de Araújo

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