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论文题目: The kinase TBK1 functions in dendritic cells to regulate T cell homeostasis, autoimmunity, and antitumor immunity
英文论文题目: The kinase TBK1 functions in dendritic cells to regulate T cell homeostasis, autoimmunity, and antitumor immunity
第一作者: Xiao, YC; Zou, Q; Xie, XP; Liu, T; Li, HYS; Jie, ZL; Jin, J; Hu, HB; Manyam, G; Zhang, L; Cheng, XH; Wang, H; Marie, I; Levy, DE; Watowich, SS; Sun, SC
英文第一作者: Xiao, YC; Zou, Q; Xie, XP; Liu, T; Li, HYS; Jie, ZL; Jin, J; Hu, HB; Manyam, G; Zhang, L; Cheng, XH; Wang, H; Marie, I; Levy, DE; Watowich, SS; Sun, SC
联系作者: Sun, SC (reprint author), Univ Texas Houston, MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA.
英文联系作者: Sun, SC (reprint author), Univ Texas Houston, MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA.
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发表年度: 2017
卷: 214
期: 5
页码: 1493-1507
摘要: 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.
英文摘要: 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.
刊物名称: JOURNAL OF EXPERIMENTAL MEDICINE
英文刊物名称: JOURNAL OF EXPERIMENTAL MEDICINE
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学科: Immunology; Medicine, Research & Experimental
英文学科: Immunology; Medicine, Research & Experimental
影响因子: 11.991
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论文类别: Article
英文论文类别: Article
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