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Oncotarget. 2016 Sep 6;7(36):57593-57605. doi: 10.18632/oncotarget.11419.

Downregulation of the phosphatase JKAP/DUSP22 in T cells as a potential new biomarker of systemic lupus erythematosus nephritis.

Chuang HC1, Chen YM2,3,4, Hung WT2, Li JP1, Chen DY2,3,4, Lan JL5,6, Tan TH1,7,8.

Author information

Immunology Research Center, National Health Research Institutes, Zhunan, Taiwan.
Division of Allergy, Immunology, and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan.
Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
School of Medicine, China Medical University Hospital, Taichung, Taiwan.
Division of Rheumatology and Immunology, China Medical University Hospital, Taichung, Taiwan.
Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan.
Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA.


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.


DUSP22; Immune response; Immunity; Immunology and Microbiology Section; JKAP; SLE; T cells; nephritis

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