國家衛生研究院 NHRI:Item 3990099045/13162
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    題名: The role of novel E3 ubiquitin ligase in the regulation of TLR3 signaling pathway
    作者: Lin, YS;Chang, YC;Lai, TY;Lee, CY;Chuang, SH;Hsu, LC
    貢獻者: Immunology Research Center
    摘要: Toll-like receptors (TLRs) are critical players in the host’s defense against infection by recognizing pathogen-associated molecular patterns (PAMPs) derived from microbes, and subsequently induce inflammatory responses, which eventually eliminate pathogens and repair damage tissues. However, excessive inflammation is detrimental to the host, and has been associated with the pathogenesis of various inflammatory and autoimmune diseases. Ubiquitination is a crucial strategy to alter protein function, expression, or cellular localization at the post-translational level, and has been shown to participate in the regulation of innate immune responses. We previously found that a novel E3 ubiquitin ligase was induced upon endosomal TLRs (TLR3/7/9) activation. In this project, we demonstrate that this E3 ubiquitin ligase negatively regulates TLR3-driven immune responses, which is dependent on its ubiquitin ligase activity. This novel E3 ubiquitin ligase controls TLR3 trafficking from the endosomes to the lysosomes for degradation. In addition, this E3 ubiquitin ligase interacts with TLR3 and promotes the ubiquitination of TLR3. We also found that lysosomal activity and intracellular pH value were altered in macrophages lacking this E3 ubiquitin ligase after poly(I:C) stimulation. Furthermore, we showed that mice with this E3 ubiquitin ligase deficiency were resistant to encephalomyocarditis virus (EMCV) infection due to enhanced type I interferon production. Our study together reveals this novel E3 ubiquitin ligase as a negative regulator of TLR3-induced inflammatory responses and proposes a novel mechanism for the termination of TLR3 signaling and immune response.
    日期: 2020-05
    關聯: Journal of Immunology. 2020 May;204(1, Suppl.):Meeting Abstract 226.26.
    Link to: https://www.jimmunol.org/content/204/1_Supplement/226.26
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-1767&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000589972402435
    顯示於類別:[莊宗顯] 會議論文/會議摘要

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