The kinase TBK1 functions in dendritic cells to regulate T cell homeostasis, autoimmunity, and antitumor immunity
The kinase TBK1 functions in dendritic cells to regulate T cell homeostasis, autoimmunity, and antitumor immunity
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激酶 TBK1 在树突状细胞中发挥作用，调节 T 细胞稳态、自身免疫和抗肿瘤免疫
DOI：
10.1084/jem.20161524
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发表时间：
2017-05-01
影响因子：
15.3
通讯作者：
Sun, Shao-Cong
中科院分区：
文献类型：
--
作者：
Xiao, Yichuan;Zou, Qiang;Sun, Shao-Cong
树突状细胞（DC）是介导免疫反应的关键，但当失调时，也会导致免疫紊乱，如自身免疫。DCs功能的分子机制还不完全清楚。在这项研究中，我们已经确定了TANK结合激酶1（TBK1），一种主要的先天免疫激酶，作为DC功能的重要调节因子。Tbk1的DC特异性缺失导致T细胞活化和自身免疫症状，并且还在癌症免疫治疗的动物模型中增强抗肿瘤免疫。TBK1缺陷型DC具有上调的共刺激分子表达和增加的T细胞引发活性。我们进一步证明，TBK1负调节诱导的一个子集的基因的I型干扰素受体（IFNAR）。在DC条件性Tbk1敲除小鼠中，IFNAR1的缺失可以在很大程度上防止异常T细胞活化和自身免疫。这些发现鉴定了TBK1在维持免疫稳态和耐受性中的DC特异性功能。
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.