title: Dectin-1-activated dendritic cells trigger potent antitumour immunity through the induction of Th9 cells.
abstract: Dectin-1 signalling in dendritic cells (DCs) has an important role in triggering protective antifungal Th17 responses. However, whether dectin-1 directs DCs to prime antitumour Th9 cells remains unclear. Here, we show that DCs activated by dectin-1 agonists potently promote naive CD4(+) T cells to differentiate into Th9 cells. Abrogation of dectin-1 in DCs completely abolishes their Th9-polarizing capability in response to dectin-1 agonist curdlan. Notably, dectin-1 stimulation of DCs upregulates TNFSF15 and OX40L, which are essential for dectin-1-activated DC-induced Th9 cell priming. Mechanistically, dectin-1 activates Syk, Raf1 and NF-κB signalling pathways, resulting in increased p50 and RelB nuclear translocation and TNFSF15 and OX40L expression. Furthermore, immunization of tumour-bearing mice with dectin-1-activated DCs induces potent antitumour response that depends on Th9 cells and IL-9 induced by dectin-1-activated DCs in vivo. Our results identify dectin-1-activated DCs as a powerful inducer of Th9 cells and antitumour immunity and may have important clinical implications.
authors: Department of Cancer Immunology, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, China.
authors: Yinghua
authors: Y
authors: Zhao
authors: Department of Cancer Immunology, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, China.
authors: Xiao
authors: X
authors: Chu
authors: Department of Cancer Immunology, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, China.
authors: Jintong
authors: J
authors: Chen
authors: Department of Cancer Immunology, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, China.
authors: Ying
authors: Y
authors: Wang
authors: Cancer Center of the First Hospital of Jilin University, Changchun 130061, China.
authors: Sujun
authors: S
authors: Gao
authors: Department of Cancer Immunology, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, China.
authors: Yuxue
authors: Y
authors: Jiang
authors: Cancer Center of the First Hospital of Jilin University, Changchun 130061, China.
authors: Xiaoqing
authors: X
authors: Zhu
authors: Department of Cancer Immunology, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, China.
authors: Guangyun
authors: G
authors: Tan
authors: The First Hospital and Institute of Immunology, Jilin University, Changchun 130061, China.
authors: Wenjie
authors: W
authors: Zhao
authors: The First Hospital and Institute of Immunology, Jilin University, Changchun 130061, China.
authors: Huanfa
authors: H
authors: Yi
authors: Laboratory of Virology, National Vaccine and Serum Institute, Beijing 100176, China.
authors: Honglin
authors: H
authors: Xu
authors: Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
authors: Xingzhe
authors: X
authors: Ma
authors: Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
authors: Yong
authors: Y
authors: Lu
authors: Department of Cancer Immunology, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, China.|Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
authors: Qing
authors: Q
authors: Yi
authors: Department of Cancer Immunology, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, China.
authors: Siqing
authors: S
authors: Wang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D045142:Cross-Priming / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007109:Immunity / Q000187:drug effects; D037181:Lectins, C-Type / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism*; D053278:OX40 Ligand / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000072377:Syk Kinase / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology*; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000378:metabolism; D047071:beta-Glucans / Q000494:pharmacology; D000099181:Dectin-1
chemical_list: D018925:Chemokines; D037181:Lectins, C-Type; D016328:NF-kappa B; D053278:OX40 Ligand; D019908:Proto-Oncogene Proteins c-raf; D000072377:Syk Kinase; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D047071:beta-Glucans; D000099181:Dectin-1; C505947:Tnfsf15 protein, mouse; C038459:curdlan