title: NKG2D ligand RAE1ε induces generation and enhances the inhibitor function of myeloid-derived suppressor cells in mice.
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.
authors.affiliation: Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, China.|Translational Medicine Research Institute of Yangzhou University, Yangzhou, China.|Jiangsu Key Laboratory of Zoonosis/Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.|Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Qian
authors.affiliation: Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, China.|Translational Medicine Research Institute of Yangzhou University, Yangzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, China.|Translational Medicine Research Institute of Yangzhou University, Yangzhou, China.
authors.forename: Shaoqing
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, China.
authors.forename: Weijuan
authors.initials: W
authors.lastname: Gong
authors.affiliation: Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ye
authors.affiliation: Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, China.
authors.forename: Jingjuan
authors.initials: J
authors.lastname: Ding
authors.affiliation: Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, China.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, China.|Translational Medicine Research Institute of Yangzhou University, Yangzhou, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Tian
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008024:Ligands; D008807:Mice, Inbred BALB C; D000072737:Myeloid-Derived Suppressor Cells / Q000378:metabolism*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D009369:Neoplasms / Q000473:pathology; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism*
chemical_list: D039481:CD11b Antigen; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K; D034521:Nuclear Matrix-Associated Proteins; D029543:Nucleocytoplasmic Transport Proteins; C490521:Rae1 protein, mouse; D016753:Interleukin-10; D015847:Interleukin-4
keywords: IL-10; NKG2D; immunosuppression; myeloid-derived suppressor cells