Dual-specificity phosphatases 22-deficient T cells contribute to the pathogenesis of ankylosing spondylitis

BMC Medicine

Research Article

Yi-Chen Yeh¹  Chung-Tei Chou²  Ming-Han Chen³  Huai-Chia Chuang⁴  Tse-Hua Tan⁵ 

[1] Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan;Division of Allergy, Immunology & Rheumatology, Taipei Veterans General Hospital, Taipei, Taiwan;Division of Allergy, Immunology & Rheumatology, Taipei Veterans General Hospital, Taipei, Taiwan;Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan;Immunology Research Center, National Health Research Institutes, Zhunan, Taiwan;Immunology Research Center, National Health Research Institutes, Zhunan, Taiwan;Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA;

关键词: DUSP22;    Ankylosing spondylitis;    Tumor necrosis factor-α;    Interferon-γ;    Interleukin-17A;   

DOI  :  10.1186/s12916-023-02745-6

 received in 2022-06-26, accepted in 2023-01-19,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundDual-specificity phosphatases (DUSPs) can dephosphorylate both tyrosine and serine/threonine residues of their substrates and regulate T cell-mediated immunity and autoimmunity. The aim of this study was to investigate the potential roles of DUSPs in ankylosing spondylitis (AS).MethodsSixty AS patients and 45 healthy controls were enrolled in this study. Associations of gene expression of 23 DUSPs in peripheral T cells with inflammatory cytokine gene expression and disease activity of AS were analyzed. Finally, we investigated whether the characteristics of AS are developed in DUSP-knockout mice.ResultsThe mRNA levels of DUSP4, DUSP5, DUSP6, DUSP7, and DUSP14 in peripheral T cells were significantly higher in AS group than those of healthy controls (all p < 0.05), while DUSP22 (also named JKAP) mRNA levels were significantly lower in AS group than healthy controls (p < 0.001). The mRNA levels of DUSP4, DUSP5, DUSP6, DUSP7, and DUSP14 in T cells were positively correlated with mRNA levels of tumor necrosis factor-α (TNF-α), whereas DUSP22 was inversely correlated (all p < 0.05). In addition, inverse correlations of DUSP22 gene expression in peripheral T cells with C-reactive protein, erythrocyte sedimentation rate, and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were observed (all p < 0.05). More importantly, aged DUSP22 knockout mice spontaneously developed syndesmophyte formation, which was accompanied by an increase of TNF-α+, interleukin-17A+, and interferon-γ+ CD3+ T cells.ConclusionsDUSP22 may play a crucial role in the pathogenesis and regulation of disease activity of AS.

【 授权许可】

CC BY   
© The Author(s) 2023

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