國家衛生研究院 NHRI:Item 3990099045/12671
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    题名: T-cell signaling in Th17-mediated inflammation
    作者: Tan, TH;Chuang, HC
    贡献者: Immunology Research Center
    摘要: MAP kinase kinase kinase kinases (MAP4Ks) are a subfamily of mammalian Ste20-like serine/threonine kinases that activate the JNK kinase cascade. We have cloned and characterized three MAP4Ks, namely HPK1 (MAP4K1), GLK (MAP4K3) and HGK (MAP4K4). Epigenetic downregulation of HGK (MAP4K4) in T cell results in differentiation of IL-6+ Th17 cells, which play important roles in the pathogenesis of Asia-prevalent non-obese T2D. HPK1 (MAP4K1) is a negative regulator of T-cell signaling through phosphorylation and sequential ubiquitination of the T-cell adaptor SLP-76. GLK (MAP4K3) also interacts with SLP-76 but does not negatively regulate SLP-76. GLK activates PKC-θ during TCR signaling; GLK-deficient mice showed impaired Th17 differentiation. T-cell specific GLK transgenic mice spontaneously developed autoimmune diseases with an induction of systemic inflammation. We found that GLK signaling specifically induced IL-17A transcription in the T cells of GLK transgenic mice. We will present the data on a novel signal transduction mechanism of IL-17A transcriptional activation of AhR and RORγt by GLK in inflammatory T cells and activated T cells. In addition, we found that GLK negatively regulated differentiation and activity of Treg cells through IKKβ. Collectively, MAP4K3/GLK plays a critical role in IL-17A-induced inflammation.
    日期: 2019-05
    關聯: Journal of Immunology. 2019 May;202(1, Suppl. S):Meeting Abstract 124.7.
    Link to: https://www.jimmunol.org/content/202/1_Supplement/124.7
    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:000524982501002
    显示于类别:[譚澤華] 會議論文/會議摘要
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