Open AccessMyeloid cell TBK1 restricts inflammatory responses
Author(s) -
Tianxiao Gao,
Ting Liu,
Chun-Jung Ko,
Lingyun Zhang,
Donghyun Joo,
Xiaoping Xie,
Lele Zhu,
Yanchuan Li,
Xuhong Cheng,
ShaoCong Sun
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2107742119
Subject(s) - proinflammatory cytokine , inflammation , tank binding kinase 1 , medicine , immunology , cancer research , microbiology and biotechnology , biology , kinase , protein kinase a , map kinase kinase kinase
Significance Macrophages play a crucial role in chronic inflammatory diseases, such as nonalcoholic steatohepatitis (NASH) and inflammatory bowel disease, but how the proinflammatory function of macrophages is controlled is not well understood. In this work, we identified TBK1 as a pivotal anti-inflammatory factor in macrophages that restricts inflammation in different disease models. Myeloid cell–specific TBK1 deficiency causes spontaneous development of metabolic disorders in aged mice and exacerbates high-fat diet–induced fatty liver disease with NASH-like symptoms. TheTbk1 -MKO mice are also hypersensitive to experimental colitis. We obtained genetic evidence that TBK1 is crucial for controlling proinflammatory signaling pathway in macrophages. These findings establish TBK1 as a pivotal anti-inflammatory factor and a potential therapeutic target for the treatment of inflammatory diseases.