Natural Killer Dendritic Cells Enhance Immune Responses Elicited byα-Galactosylceramide-Stimulated Natural Killer T Cells

Sung Won Lee,Nayoung Kim,Hyun Jung Park,Seokmann Hong

doi:10.1155/2013/460706

Sung Won Lee, Nayoung Kim + Show 2 more

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https://doi.org/10.1155/2013/460706

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Abstract

Natural killer dendritic cells (NKDCs) possess potent anti-tumor activity, but the cellular effect of NKDC interactions with other innate immune cells is unclear. In this study, we demonstrate that the interaction of NKDCs and natural killer T (NKT) cells is required for the anti-tumor immune responses that are elicited by α-galactosylceramide (α-GC) in mice. The rapid and strong expression of interferon-γ by NKDCs after α-GC stimulation was dependent on NKT cells. Various NK and DC molecular markers and cytotoxic molecules were up-regulated following α-GC administration. This up-regulation could improve NKDC presentation of tumor antigens and increase cytotoxicity against tumor cells. NKDCs were required for the stimulation of DCs, NK cells, and NKT cells. The strong anti-tumor immune responses elicited by α-GC may be due to the down-regulation of regulatory T cells. Furthermore, the depletion of NKDCs dampened the tumor clearance mediated by α-GC-stimulated NKT cells in vivo. Taken together, these results indicate that complex interactions of innate immune cells might be required to achieve optimal anti-tumor immune responses during the early stages of tumorigenesis.

Highlights

The importance of communication among innate immune cells has recently been emphasized in various immunity models
Previous studies have demonstrated that α-GC-stimulated natural killer T (NKT) cells induce the activation of dendritic cells (DCs) and natural killer (NK) cells, it was not clear whether activated NKT cells could stimulate Natural killer dendritic cells (NKDCs)
NKDCs and DCs from Vα14 Tcell receptor (TCR) Tg mice expressed more MHC class II and co-stimulatory molecules, as expected. These results suggest that NKDC maturation induced by α-GC requires NKT cells, implying that NKT cells play a necessary role in the development of NKDCs but not in the development of DCs

Summary

Introduction

The importance of communication among innate immune cells has recently been emphasized in various immunity models. The interaction between dendritic cells (DCs) and natural killer (NK) cells influences both the innate and adaptive immune responses in anti-tumor and antimicrobial immunity [1]. DCs are specialized cells that engage in phagocytosis, antigen presentation, and the production of specific cytokines, including type I interferon (IFN) and interleukin (IL)-12, whereas NK cells can be cytolytic and secrete different cytokines, including IFN-γ, tumor necrosis factor (TNF)-α, and granulocyte-macrophage colonystimulating factor (GM-CSF). NK cells are activated by the cytokines from DCs as well as by direct cell-cell contacts. NK cells can induce DC maturation, which is important for optimal anti-tumor immunity. NK cells can kill immature DCs. NK cells might regulate DC homeostasis

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