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Tob2 Inhibits TLR-Induced Inflammatory Responses by Association with TRAF6 and MyD88
The Journal of Immunology ( IF 4.4 ) Pub Date : 2020-07-01 , DOI: 10.4049/jimmunol.2000057
Guosheng Jiang 1 , Mouchun Gong 2 , Hui Song 3 , Wangnan Sun 4 , Wei Zhao 3 , Lijuan Wang 5
Affiliation  

Key Points Tob2 inhibits TLR-induced proinflammatory cytokine expression. Tob2 negatively regulates TLR4-induced NF-κB and MAPK activation. Tob2 interacts with TRAF6 and MyD88 and inhibits signaling from them. Optimal activation of TLR pathways is crucial for the initiation of inflammatory responses and eliminating invading micro-organisms. However, excessive of TLR activation may lead to autoimmune and inflammatory diseases. Thus, TLR pathways should be tightly controlled. In this study, we identify Tob2, a Tob/BTG family member, as a suppressor of TLR pathways. Tob2 deficiency enhances TLR-induced NF-κB and MAPK activation and promotes the expression of proinflammatory cytokines in primary peritoneal macrophages of C57BL/6 mice. Furthermore, Tob2-defective C57BL/6 mice may be more susceptible to endotoxemic shock in vivo. Mechanistically, Tob2 interacts with TRAF6 and MyD88 and thus inhibits signaling from the MyD88–TRAF6 complex in primary peritoneal macrophages and HEK293T cells. Therefore, our results uncover a regulatory mechanism of TLR pathways and provide a potential target for the intervention of diseases with excessive TLR activation.

中文翻译:

Tob2 通过与 TRAF6 和 MyD88 的关联抑制 TLR 诱导的炎症反应

关键点 Tob2 抑制 TLR 诱导的促炎细胞因子表达。Tob2 负向调节 TLR4 诱导的 NF-κB 和 MAPK 激活。Tob2 与 TRAF6 和 MyD88 相互作用并抑制来自它们的信号。TLR 通路的最佳激活对于启动炎症反应和消除入侵微生物至关重要。然而,过度的 TLR 激活可能导致自身免疫和炎症性疾病。因此,应严格控制 TLR 途径。在这项研究中,我们将 Tob/BTG 家族成员 Tob2 鉴定为 TLR 通路的抑制因子。Tob2 缺乏会增强 TLR 诱导的 NF-κB 和 MAPK 活化,并促进 C57BL/6 小鼠原代腹膜巨噬细胞中促炎细胞因子的表达。此外,Tob2 缺陷的 C57BL/6 小鼠在体内可能更容易受到内毒素休克的影响。从机制上讲,Tob2 与 TRAF6 和 MyD88 相互作用,从而抑制原代腹膜巨噬细胞和 HEK293T 细胞中 MyD88-TRAF6 复合物的信号传导。因此,我们的研究结果揭示了 TLR 通路的调控机制,并为干预过度 TLR 激活的疾病提供了潜在的靶点。
更新日期:2020-07-01
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