title: The kinase TBK1 functions in dendritic cells to regulate T cell homeostasis, autoimmunity, and antitumor immunity.
abstract: Dendritic cells (DCs) are crucial for mediating immune responses but, when deregulated, also contribute to immunological disorders, such as autoimmunity. The molecular mechanism underlying the function of DCs is incompletely understood. In this study, we have identified TANK-binding kinase 1 (TBK1), a master innate immune kinase, as an important regulator of DC function. DC-specific deletion ofTbk1causes T cell activation and autoimmune symptoms and also enhances antitumor immunity in animal models of cancer immunotherapy. The TBK1-deficient DCs have up-regulated expression of co-stimulatory molecules and increased T cell-priming activity. We further demonstrate that TBK1 negatively regulates the induction of a subset of genes by type I interferon receptor (IFNAR). Deletion of IFNAR1 could largely prevent aberrant T cell activation and autoimmunity in DC-conditionalTbk1knockout mice. These findings identify a DC-specific function of TBK1 in the maintenance of immune homeostasis and tolerance.
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai 200031, China.|Department of Immunology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030.
authors.forename: Yichuan
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Immunology and Microbiology, Shanghai Institute of Immunology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.|Department of Immunology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030.
authors.forename: Qiang
authors.identifier: 0000-0002-5115-4283
authors.initials: Q
authors.lastname: Zou
authors.affiliation: Department of Immunology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Immunology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030.|State Key Laboratory of Biotherapy, West China Hospital, Si-Chuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Immunology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030.
authors.forename: Haiyan S
authors.identifier: 0000-0001-5069-9735
authors.initials: HS
authors.lastname: Li
authors.affiliation: Department of Immunology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030.
authors.forename: Zuliang
authors.initials: Z
authors.lastname: Jie
authors.affiliation: Department of Immunology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030.|Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.
authors.forename: Jin
authors.identifier: 0000-0001-7887-5972
authors.initials: J
authors.lastname: Jin
authors.affiliation: Department of Immunology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030.|State Key Laboratory of Biotherapy, West China Hospital, Si-Chuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
authors.forename: Hongbo
authors.identifier: 0000-0002-6465-4340
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030.
authors.forename: Ganiraju
authors.initials: G
authors.lastname: Manyam
authors.affiliation: Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030.|Department of Environmental Health, University of Cincinnati, Cincinnati, OH 45220.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Immunology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030.
authors.forename: Xuhong
authors.identifier: 0000-0003-2498-3059
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Immunology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030.
authors.forename: Hui
authors.identifier: 0000-0002-8706-2217
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, NY 10016.|Department of Microbiology, NYU School of Medicine, New York, NY 10016.|NYU Cancer Institute, NYU School of Medicine, New York, NY 10016.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Marie
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, NY 10016.
authors.forename: David E
authors.identifier: 0000-0002-7320-7788
authors.initials: DE
authors.lastname: Levy
authors.affiliation: Department of Immunology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030.|Graduate School of Biomedical Sciences, The University of Texas, Houston, TX 77030.
authors.forename: Stephanie S
authors.identifier: 0000-0003-1969-659X
authors.initials: SS
authors.lastname: Watowich
authors.affiliation: Department of Immunology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030 ssun@mdanderson.org.|Graduate School of Biomedical Sciences, The University of Texas, Houston, TX 77030.
authors.forename: Shao-Cong
authors.identifier: 0000-0001-7353-9400
authors.initials: SC
authors.lastname: Sun
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000502:physiology*; D003713:Dendritic Cells / Q000502:physiology*; D006706:Homeostasis; D008213:Lymphocyte Activation / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000276:immunology* / Q000503:physiopathology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D050796:STAT3 Transcription Factor / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C498588:Tbk1 protein, mouse; D017346:Protein Serine-Threonine Kinases