https://scholars.lib.ntu.edu.tw/handle/123456789/616298
標題: | Myeloid cell TBK1 restricts inflammatory responses | 作者: | Gao, Tianxiao Liu, Ting Chun-Jung Ko Zhang, Lingyun Joo, Donghyun Xie, Xiaoping Zhu, Lele Li, Yanchuan Cheng, Xuhong Sun, Shao-Cong |
關鍵字: | TBK1; fatty liver disease; inflammation; macrophages; metabolic disorders | 公開日期: | 2022 | 出版社: | NATL ACAD SCIENCES | 卷: | 119 | 期: | 4 | 來源出版物: | Proceedings of the National Academy of Sciences of the United States of America | 摘要: | Proinflammatory cytokine production by innate immune cells plays a crucial role in inflammatory diseases, but the molecular mechanisms controlling the inflammatory responses are poorly understood. Here, we show that TANK-binding kinase 1 (TBK1) serves as a vital regulator of proinflammatory macrophage function and protects against tissue inflammation. Myeloid cell-conditional Tbk1 knockout (MKO) mice spontaneously developed adipose hypertrophy and metabolic disorders at old ages, associated with increased adipose tissue M1 macrophage infiltration and proinflammatory cytokine expression. When fed with a high-fat diet, the Tbk1-MKO mice also displayed exacerbated hepatic inflammation and insulin resistance, developing symptoms of nonalcoholic steatohepatitis. Furthermore, myeloid cell-specific TBK1 ablation exacerbates inflammation in experimental colitis. Mechanistically, TBK1 functions in macrophages to suppress the NF-κB and MAP kinase signaling pathways and thus attenuate induction of proinflammatory cytokines, particularly IL-1β. Ablation of IL-1 receptor 1 (IL-1R1) eliminates the inflammatory symptoms of Tbk1-MKO mice. These results establish TBK1 as a pivotal anti-inflammatory mediator that restricts inflammation in different disease models. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/616298 | ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.2107742119 |
顯示於: | 免疫學研究所 |
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