2022年6月14日 · We find that CXCL4 modulates the TLR8 response by synergistically activating TBK1 and IRF5 signaling, and by remodeling the epigenome to regulate transcriptional responses to TLR8 signaling.

NF-κB and IFN Regulatory Factor 5 (IRF5) are required for the transcription of many proinflammatory cytokines in myeloid cells. The protein kinase IKKβ is the major activator of NF-κB but how IRF5 is activated has been unclear. This paper demonstrates that IKKβ also activates IRF5 by catalyzing the phosphorylation of Ser462.

从机制上讲，cxcl4 和 tlr8 的共刺激协同激活 tbk1 和 ikkε，通过与 irf5 偶联将这些激酶重新用于炎症反应，并激活 nlrp3 炎症小体。 CXCL4 信号传导以与 TLR8 合作和协同的方式诱导染色质重塑并激活与炎症基因相关的从头增强子。

2019年11月1日 · These results elucidate a new mechanism between IRF5 and TBK1 during the innate immune activation in vertebrates: bcIRF5 inhibits bcTBK1-mediated IFN signaling; however, it correlates with bcTBK1 and triggers cell death to …

2005年4月29日 · TBK1 and IKKϵ Phosphorylate IRF5 in Vitro—The IKK-related kinases, IKKϵ and TBK1, are essential regulators of the IFN response (31, 32, 33). They both phosphorylate and activate IRF3 and IRF7 (34, 36). Their role in IRF5 activation has not yet been addressed. We, therefore, investigated if IRF5 was also a target of TBK1 kinase activity in ...

2018年9月10日 · Phosphorylation of IRF5 by TBK1 or IKKε fail to induce nuclear translocation of IRF5 . Furthermore, macrophages from TBK1-deficient mice produce normal levels of proinflammatory cytokines in response to LPS . Thus, these kinases can be excluded as suitable IRF5 candidate kinases.

2023年1月1日 · A recent study revealed important roles for IRF5 and TBK1 in innate immune activation, and IRF5 negatively regulates TBK1-mediated IFN signalling (Yang et al., 2019). To investigate whether IRF5 deficiency increased the level of TBK1, thus exerting a protective effect on TDP-25 cells, we first evaluated TBK1 expression after IRF5 knockdown in ...

IRF5 knockdown using a lentivirus carrying an shRNA in TDP-25 cells exerted a protective effect and reduced the level of the apoptosis-related protein cleaved caspase-9 and the cell cycle arrest protein p21, while increasing the expression of the antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and its target ...

2024年10月22日 · irf5 缺失逆转了 tbk1 抑制对 m-csf 介导的巨噬细胞极化的影响。 我们的研究结果表明，TBK1 部分通过 IRF5/IRF4 轴响应 M-CSF 刺激，有助于巨噬细胞极化的调节。

2022年6月14日 · Mechanistically, costimulation by CXCL4 and TLR8 synergistically activates TBK1 and IKKε, repurposes these kinases towards an inflammatory response via coupling with IRF5, and activates the NLRP3 inflammasome.