Tob2 Inhibits TLR-Induced Inflammatory Responses by Association with TRAF6 and MyD88.

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. Copyright © 2020 by The American Association of Immunologists, Inc.

Citation

Guosheng Jiang, Mouchun Gong, Hui Song, Wangnan Sun, Wei Zhao, Lijuan Wang. Tob2 Inhibits TLR-Induced Inflammatory Responses by Association with TRAF6 and MyD88. Journal of immunology (Baltimore, Md. : 1950). 2020 Aug 15;205(4):981-986

Mesh Tags

Substances

PMID: 32611726

search → result