國家衛生研究院 NHRI:Item 3990099045/7579
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    NHRI > Immunology Research Center > Tse-Hua Tan > Periodical Articles >  Item 3990099045/7579


    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/7579


    Title: Germinal center kinase-like kinase overexpression in T cells as a novel biomarker in rheumatoid arthritis
    Authors: Chen, YM;Chuang, HC;Lin, WC;Tsai, CY;Wu, CW;Gong, NR;Hung, WT;Lan, TH;Lan, JL;Tan, TH;Chen, DY
    Contributors: Immunology Research Center
    Abstract: ObjectiveGerminal center kinase-like kinase (GLK; also called MAPKKKK-3) activates protein kinase C (PKC) during T cell activation and controls autoimmunity in lupus patients. Intracellular kinases are involved in the pathogenesis of rheumatoid arthritis (RA). We undertook this study to determine the role of GLK in RA. MethodsThe severity of collagen-induced arthritis (CIA) was studied in GLK-deficient mice. Expression levels of GLK from RA patients were determined by Western blotting, flow cytometry, real-time polymerase chain reaction, and immunohistochemical staining. Localization of GLK in T cells was identified by confocal microscopy. RA disease activity was assessed using the Disease Activity Score in 28 joints. ResultsGLK-deficient mice displayed impaired CIA development and decreased inflammatory cytokine levels. Local T cell infiltration and collagen restimulation responses were impaired by GLK deficiency. RA patients showed significantly higher GLK protein and messenger RNA levels in peripheral blood T cells than did healthy controls. GLK-overexpressing T cells in synovial fluid and synovial tissue samples from RA patients were increased compared with those from osteoarthritis patients. Confocal microscopy and flow cytometry showed that GLK colocalized and coexisted with phosphorylated PKC in T cells from RA patients. Frequencies of GLK-expressing T cells were significantly correlated with RA disease activity. ConclusionGLK overexpression in T cells contributes to the pathogenesis of RA, indicating that GLK is a novel biomarker for autoimmune disease severity and a potential therapeutic target for RA.
    Date: 2013-10
    Relation: Arthritis and Rheumatism. 2013 Oct;65(10):2573-2582.
    Link to: http://dx.doi.org/10.1002/art.38067
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000325136600011
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84885121132
    Appears in Collections:[Tse-Hua Tan] Periodical Articles
    [Huai-Chia Chuang] Periodical Articles

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