NKG2D ligand RAE1ε induces generation and enhances the inhibitor function of myeloid‐derived suppressor cells in mice |
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Authors: | Li Qian Weijuan Gong Xiaoqin Jia Lu Liu Feng Ye Jingjuan Ding Yuwei Xu Yi Fu Fang Tian |
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Affiliation: | 1. Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, China;2. Translational Medicine Research Institute of Yangzhou University, Yangzhou, China;3. Jiangsu Key Laboratory of Zoonosis/Jiangsu Co‐innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China;4. Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, ChinaThese authors contributed equally to this study. |
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Abstract: | 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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Keywords: | NKG2D myeloid‐derived suppressor cells IL‐10 immunosuppression |
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