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NKG2D ligand RAE1ε induces generation and enhances the inhibitor function of myeloid‐derived suppressor cells in mice

Expression of surface NKG2D ligands on tumour cells, which activates nature killer (NK) cells and CD8(+) T cells, is crucial in antitumour immunity. Some types of tumours have evolved mechanisms to suppress NKG2D‐mediated immune cell activation, such as tumour‐derived soluble NKG2D ligands or sustai...

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Autores principales: Qian, Li, Liu, Yang, Wang, Shaoqing, Gong, Weijuan, Jia, Xiaoqin, Liu, Lu, Ye, Feng, Ding, Jingjuan, Xu, Yuwei, Fu, Yi, Tian, Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5571551/
https://www.ncbi.nlm.nih.gov/pubmed/28276625
http://dx.doi.org/10.1111/jcmm.13124
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author Qian, Li
Liu, Yang
Wang, Shaoqing
Gong, Weijuan
Jia, Xiaoqin
Liu, Lu
Ye, Feng
Ding, Jingjuan
Xu, Yuwei
Fu, Yi
Tian, Fang
author_facet Qian, Li
Liu, Yang
Wang, Shaoqing
Gong, Weijuan
Jia, Xiaoqin
Liu, Lu
Ye, Feng
Ding, Jingjuan
Xu, Yuwei
Fu, Yi
Tian, Fang
author_sort Qian, Li
collection PubMed
description Expression of surface NKG2D ligands on tumour cells, which activates nature killer (NK) cells and CD8(+) T cells, is crucial in antitumour immunity. Some types of tumours have evolved mechanisms to suppress NKG2D‐mediated immune cell activation, such as tumour‐derived soluble NKG2D ligands or sustained NKG2D ligands produced by tumours down‐regulate the expression of NKG2D on NK cells and CD8(+) T cells. Here, we report that surface NKG2D ligand RAE1ε on tumour cells induces CD11b(+)Gr‐1(+) myeloid‐derived suppressor cell (MDSC) via NKG2D in vitro and in vivo. MDSCs induced by RAE1ε display a robust induction of IL‐10 and arginase, and these MDSCs show greater suppressive activity by inhibiting antigen‐non‐specific CD8(+) T‐cell proliferation. Consistently, upon adoptive transfer, MDSCs induced by RAE1ε significantly promote CT26 tumour growth in IL‐10‐ and arginase‐dependent manners. RAE1ε moves cytokine balance towards Th2 but not Th1 in vivo. Furthermore, RAE1ε enhances inhibitory function of CT26‐derived MDSCs and promotes IL‐4 rather than IFN‐γ production from CT26‐derived MDSCs through NKG2D in vitro. Our study has demonstrated a novel mechanism for NKG2D ligand(+) tumour cells escaping from immunosurveillance by facilitating the proliferation and the inhibitory function of MDSCs.
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spelling pubmed-55715512017-09-01 NKG2D ligand RAE1ε induces generation and enhances the inhibitor function of myeloid‐derived suppressor cells in mice Qian, Li Liu, Yang Wang, Shaoqing Gong, Weijuan Jia, Xiaoqin Liu, Lu Ye, Feng Ding, Jingjuan Xu, Yuwei Fu, Yi Tian, Fang J Cell Mol Med Original Articles Expression of surface NKG2D ligands on tumour cells, which activates nature killer (NK) cells and CD8(+) T cells, is crucial in antitumour immunity. Some types of tumours have evolved mechanisms to suppress NKG2D‐mediated immune cell activation, such as tumour‐derived soluble NKG2D ligands or sustained NKG2D ligands produced by tumours down‐regulate the expression of NKG2D on NK cells and CD8(+) T cells. Here, we report that surface NKG2D ligand RAE1ε on tumour cells induces CD11b(+)Gr‐1(+) myeloid‐derived suppressor cell (MDSC) via NKG2D in vitro and in vivo. MDSCs induced by RAE1ε display a robust induction of IL‐10 and arginase, and these MDSCs show greater suppressive activity by inhibiting antigen‐non‐specific CD8(+) T‐cell proliferation. Consistently, upon adoptive transfer, MDSCs induced by RAE1ε significantly promote CT26 tumour growth in IL‐10‐ and arginase‐dependent manners. RAE1ε moves cytokine balance towards Th2 but not Th1 in vivo. Furthermore, RAE1ε enhances inhibitory function of CT26‐derived MDSCs and promotes IL‐4 rather than IFN‐γ production from CT26‐derived MDSCs through NKG2D in vitro. Our study has demonstrated a novel mechanism for NKG2D ligand(+) tumour cells escaping from immunosurveillance by facilitating the proliferation and the inhibitory function of MDSCs. John Wiley and Sons Inc. 2017-03-09 2017-09 /pmc/articles/PMC5571551/ /pubmed/28276625 http://dx.doi.org/10.1111/jcmm.13124 Text en © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Qian, Li
Liu, Yang
Wang, Shaoqing
Gong, Weijuan
Jia, Xiaoqin
Liu, Lu
Ye, Feng
Ding, Jingjuan
Xu, Yuwei
Fu, Yi
Tian, Fang
NKG2D ligand RAE1ε induces generation and enhances the inhibitor function of myeloid‐derived suppressor cells in mice
title NKG2D ligand RAE1ε induces generation and enhances the inhibitor function of myeloid‐derived suppressor cells in mice
title_full NKG2D ligand RAE1ε induces generation and enhances the inhibitor function of myeloid‐derived suppressor cells in mice
title_fullStr NKG2D ligand RAE1ε induces generation and enhances the inhibitor function of myeloid‐derived suppressor cells in mice
title_full_unstemmed NKG2D ligand RAE1ε induces generation and enhances the inhibitor function of myeloid‐derived suppressor cells in mice
title_short NKG2D ligand RAE1ε induces generation and enhances the inhibitor function of myeloid‐derived suppressor cells in mice
title_sort nkg2d ligand rae1ε induces generation and enhances the inhibitor function of myeloid‐derived suppressor cells in mice
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5571551/
https://www.ncbi.nlm.nih.gov/pubmed/28276625
http://dx.doi.org/10.1111/jcmm.13124
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