Oncotarget

Research Papers: Immunology:

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

Huai-Chia Chuang, Yi-Ming Chen, Wei-Ting Hung, Ju-Pi Li, Der-Yuan Chen, Joung-Liang Lan and Tse-Hua Tan _

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Oncotarget. 2016; 7:57593-57605. https://doi.org/10.18632/oncotarget.11419

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Abstract

Huai-Chia Chuang1,*, Yi-Ming Chen2,3,4,*, Wei-Ting Hung2, Ju-Pi Li1, Der-Yuan Chen2,3,4, Joung-Liang Lan5,6 and Tse-Hua Tan1,7,8

1 Immunology Research Center, National Health Research Institutes, Zhunan, Taiwan

2 Division of Allergy, Immunology, and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan

3 Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan

4 Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan

5 School of Medicine, China Medical University Hospital, Taichung, Taiwan

6 Division of Rheumatology and Immunology, China Medical University Hospital, Taichung, Taiwan

7 Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan

8 Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA

* These authors have contributed equally to this work

Correspondence to:

Tse-Hua Tan, email:

Joung-Liang Lan, email:

Der-Yuan Chen, email:

Keywords: JKAP, DUSP22, SLE, nephritis, T cells, Immunology and Microbiology Section, Immune response, Immunity

Received: March 04, 2016 Accepted: August 13, 2016 Published: August 19, 2016

Abstract

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.


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