國家衛生研究院 NHRI:Item 3990099045/9931
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    题名: Downregulation of the phosphatase JKAP/DUSP22 in T Cells as a potential new biomarker of systemic lupus erythematosus nephritis
    作者: Chuang, HC;Chen, YM;Hung, WT;Li, JP;Chen, DY;Lan, JL;Tan, TH
    贡献者: Immunology Research Center
    摘要: Systemic lupus erythematosus (SLE) is a complex autoimmune disease that is characterized by systemic inflammation and multiple organ failures. Dysregulation of T cells plays a critical role in SLE pathogenesis. Our previous study indicates that JKAP (also named DUSP22) inhibits T-cell activation and that JKAP knockout mice develop spontaneous autoimmunity; therefore, we investigated whether JKAP downregulation is involved in SLE patients. JKAP protein levels in purified T cells were examined by immunoblotting using blood samples from 43 SLE patients and 32 healthy controls. SLE patients showed significantly decreased JKAP protein levels in peripheral blood T cells compared to healthy controls. JKAP protein levels in peripheral blood T cells were inversely correlated with SLE disease activity index (SLEDAI) and anti-dsDNA antibody levels. JKAP downregulation in T cells was highly correlated with daily urinary protein amounts and with poor renal outcome in lupus nephritis patients. Notably, the diagnostic power of JKAP downregulation in T cells for active lupus nephritis was higher than those of serum anti-dsDNA antibody, C3, and C4 levels. Moreover, T-cell-specific transgenic mice expressing a dominant-negative JKAP mutant developed spontaneous autoimmune nephritis. Furthermore, JKAP-deficient T cells overproduced complement components, soluble ICAM-1, and soluble VCAM-1 in the kidney; these cytokines have been reported to be involved in lupus nephritis. Taken together, JKAP downregulation in T cells is a novel diagnostic and prognostic biomarker for SLE nephritis.
    日期: 2016-08
    關聯: Oncotarget. 2016 Aug;7(36):57593-57605.
    Link to: http://dx.doi.org/10.18632/oncotarget.11419
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000387153200011
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84988421971
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