國家衛生研究院 NHRI:Item 3990099045/10034
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    题名: Emerging roles of an innate immune regulator TAPE in Toll-like receptors, RIG-I-like receptors, and beyond
    作者: Ling, P;Chen, KR;Kao, CC;Chuang, HC;Tan, TH
    贡献者: Immunology Research Center
    摘要: Pattern-recognition receptors (PRRs) trigger innate immune defenses against pathogen infection via signaling pathways linking to inflammation and cell-autonomous immunity like phagocytosis and autophagy. IKK family kinases, IKKα and IKKβ, function to relay PRR signals to proinflammatory cytokine production to amplify immune responses. TBK1, a non-canonical IKK kinase, links several nucleic acid sensors to type I interferon induction against viral infection and also regulates the autophagic clearance of intracellular bacteria. TBK1-Associated Protein in Endolysosomes designated TAPE, also known as CC2D1A, is an innate immune regulator acting upstream of Trif to regulate the TLR3 and TLR4 pathways, or upstream of MAVS to regulate the cytosolic RIG-I-like receptor (RLR) pathways. Notably, TAPE is a regulator implicated in both the endosomal TLR and cytosolic RLR pathways at such an early step. We are thus interested in investigating in vivo role of TAPE in innate immunity and molecular mechanisms by which TAPE regulates TLRs, RLRs, and possibly other PRRs. TAPE conditional knockout (cKO) mice, in which TAPE is selectively disrupted in immune cells, were generated for our study. Our results showed that upon influenza A virus infection, TAPE cKO mice exhibited a more severe mortality than wild type mice. Further, TAPE cKO mice were shown to be more susceptible to Salmonella infection but more resistant to LPS-induced septic shock. Ex vivo studies showed that TAPE was implicated in the autophagic clearance of Salmonella. Together, our data support a critical role for TAPE in regulating innate immune defenses through TLRs, RLRs, and autophagy.
    日期: 2016-08
    關聯: European Journal of Immunology. 2016 Aug;46(Suppl. 1):646.
    Link to: http://dx.doi.org/10.1002/eji.201670200
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0014-2980&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000383610401488
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