PMID- 28356390 OWN - NLM STAT- MEDLINE DCOM- 20170912 LR - 20211204 IS - 1540-9538 (Electronic) IS - 0022-1007 (Print) IS - 0022-1007 (Linking) VI - 214 IP - 5 DP - 2017 May 1 TI - The kinase TBK1 functions in dendritic cells to regulate T cell homeostasis, autoimmunity, and antitumor immunity. PG - 1493-1507 LID - 10.1084/jem.20161524 [doi] AB - 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 of Tbk1 causes 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-conditional Tbk1 knockout mice. These findings identify a DC-specific function of TBK1 in the maintenance of immune homeostasis and tolerance. CI - (c) 2017 Xiao et al. FAU - Xiao, Yichuan AU - Xiao Y AD - 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. AD - Department of Immunology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030. FAU - Zou, Qiang AU - Zou Q AUID- ORCID: 0000-0002-5115-4283 AD - 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. AD - Department of Immunology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030. FAU - Xie, Xiaoping AU - Xie X AD - Department of Immunology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030. FAU - Liu, Ting AU - Liu T AD - Department of Immunology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030. AD - State Key Laboratory of Biotherapy, West China Hospital, Si-Chuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China. FAU - Li, Haiyan S AU - Li HS AUID- ORCID: 0000-0001-5069-9735 AD - Department of Immunology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030. FAU - Jie, Zuliang AU - Jie Z AD - Department of Immunology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030. FAU - Jin, Jin AU - Jin J AUID- ORCID: 0000-0001-7887-5972 AD - Department of Immunology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030. AD - Life Sciences Institute, Zhejiang University, Hangzhou 310058, China. FAU - Hu, Hongbo AU - Hu H AUID- ORCID: 0000-0002-6465-4340 AD - Department of Immunology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030. AD - State Key Laboratory of Biotherapy, West China Hospital, Si-Chuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China. FAU - Manyam, Ganiraju AU - Manyam G AD - Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030. FAU - Zhang, Li AU - Zhang L AD - Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030. AD - Department of Environmental Health, University of Cincinnati, Cincinnati, OH 45220. FAU - Cheng, Xuhong AU - Cheng X AUID- ORCID: 0000-0003-2498-3059 AD - Department of Immunology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030. FAU - Wang, Hui AU - Wang H AUID- ORCID: 0000-0002-8706-2217 AD - Department of Immunology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030. FAU - Marie, Isabelle AU - Marie I AD - Department of Pathology, NYU School of Medicine, New York, NY 10016. AD - Department of Microbiology, NYU School of Medicine, New York, NY 10016. AD - NYU Cancer Institute, NYU School of Medicine, New York, NY 10016. FAU - Levy, David E AU - Levy DE AUID- ORCID: 0000-0002-7320-7788 AD - Department of Pathology, NYU School of Medicine, New York, NY 10016. FAU - Watowich, Stephanie S AU - Watowich SS AUID- ORCID: 0000-0003-1969-659X AD - Department of Immunology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030. AD - Graduate School of Biomedical Sciences, The University of Texas, Houston, TX 77030. FAU - Sun, Shao-Cong AU - Sun SC AUID- ORCID: 0000-0001-7353-9400 AD - Department of Immunology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030 ssun@mdanderson.org. AD - Graduate School of Biomedical Sciences, The University of Texas, Houston, TX 77030. LA - eng GR - P30 CA016672/CA/NCI NIH HHS/United States GR - R01 GM084459/GM/NIGMS NIH HHS/United States PT - Journal Article DEP - 20170329 PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (STAT3 Transcription Factor) RN - 0 (Stat3 protein, mouse) RN - EC 2.7.1.- (Tbk1 protein, mouse) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) SB - IM CIN - Cell Mol Immunol. 2018 Aug;15(8):743-745. PMID: 29503440 MH - Animals MH - Autoimmunity/*physiology MH - Dendritic Cells/*physiology MH - Homeostasis MH - Lymphocyte Activation/physiology MH - Mice MH - Mice, Knockout MH - Neoplasms/*immunology/physiopathology MH - Protein Serine-Threonine Kinases/*physiology MH - STAT3 Transcription Factor/physiology MH - T-Lymphocytes/*physiology PMC - PMC5413337 EDAT- 2017/03/31 06:00 MHDA- 2017/09/13 06:00 PMCR- 2017/11/01 CRDT- 2017/03/31 06:00 PHST- 2016/09/12 00:00 [received] PHST- 2016/12/18 00:00 [revised] PHST- 2017/02/09 00:00 [accepted] PHST- 2017/03/31 06:00 [pubmed] PHST- 2017/09/13 06:00 [medline] PHST- 2017/03/31 06:00 [entrez] PHST- 2017/11/01 00:00 [pmc-release] AID - jem.20161524 [pii] AID - 20161524 [pii] AID - 10.1084/jem.20161524 [doi] PST - ppublish SO - J Exp Med. 2017 May 1;214(5):1493-1507. doi: 10.1084/jem.20161524. Epub 2017 Mar 29.