Myeloid cell TBK1 restricts inflammatory responses.
In: Proceedings of the National Academy of Sciences of the United States of America, Jg. 119 (2022-01-25), Heft 4, S. 1-11
Online
academicJournal
Zugriff:
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-1ß. 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. [ABSTRACT FROM AUTHOR]
Titel: |
Myeloid cell TBK1 restricts inflammatory responses.
|
---|---|
Autor/in / Beteiligte Person: | Gao, Tianxiao ; Liu, Ting ; Ko, Chun-Jung ; Zhang, Lingyun ; Joo, Donghyun ; Xie, Xiaoping ; Zhu, Lele ; Li, Yanchuan ; Cheng, Xuhong ; Sun, Shao-Cong |
Link: | |
Zeitschrift: | Proceedings of the National Academy of Sciences of the United States of America, Jg. 119 (2022-01-25), Heft 4, S. 1-11 |
Veröffentlichung: | 2022 |
Medientyp: | academicJournal |
ISSN: | 0027-8424 (print) |
DOI: | 10.1073/pnas.2107742119 |
Schlagwort: |
|
Sonstiges: |
|