文章基本信息

标题：Reciprocal regulation of TLR2-mediated IFN-β production by SHP2 and Gsk3β
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作者：Jin Hee Park ; Ryeojin Ko ; Soo Young Lee 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2017
卷号：7
期号：1
DOI：10.1038/s41598-017-07316-3
语种：English
出版社：Springer Nature
摘要：Toll-like receptor 2 (TLR2) mediates the innate immune response to bacterial lipopeptides and peptidoglycans by stimulating the production of inflammatory cytokines. However, the mechanisms by which TLR2 signaling regulates type I interferon (IFN)-β production are poorly understood. Here, we identified Src homology 2-containing protein tyrosine phosphatase 2 (SHP2) as a negative regulator of TLR2-induced IFN-β production. Pharmacological inhibition or reduced expression of SHP2 potentiated TLR2 agonist-mediated IFN-β transcription and STAT1 activation, whereas overexpression of SHP2 impaired IFN-β transcription and STAT1 activation. SHP2 physically associated with the glycogen synthase kinase 3β (Gsk3β) in an agonist-dependent manner. Gsk3β positively regulates transcription of IFN-β following TLR2 stimulation by inhibiting the phosphorylation of SHP2. SHP2 inhibited the transcriptional activity of IRF-1 and IRF-8 at the IFN-β promoter. Remarkably, IRF-1 and IRF-8 are recruited to the IFN-β promoter in a SHP2 phosphatase activity-dependent manner. These findings provide insight into the mechanisms by which SHP2 and Gsk3β work together to modulate TLR2-mediated IFN-β production in macrophages.