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

• Published in: BMC medicine Vol. 21; no. 1; pp. 46 - 15
• Main Authors: Chen, Ming-Han, Chuang, Huai-Chia, Yeh, Yi-Chen, Chou, Chung-Tei, Tan, Tse-Hua
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 10.02.2023; BioMed Central; BMC
• Subjects: Analysis; Animals; Ankylosing spondylitis; Arthritis; Autoimmunity; Biomarkers; C-reactive protein; Care and treatment; CD3 antigen; Cell-mediated immunity; Cloning; Correlation; Cytokines; Development and progression; Dosage and administration; Dual-Specificity Phosphatases - genetics; Dual-Specificity Phosphatases - metabolism; DUSP22; Erythrocyte sedimentation rate; Erythrocytes; Flow cytometry; Gene expression; Genetic aspects; Inflammation; Interferon gamma; Interferon-γ; Interleukin-17A; Interleukins; Kinases; Laboratories; Lymphocytes; Lymphocytes T; Mice; Mice, Knockout; Mitogen-activated protein kinases; Monoclonal antibodies; Pathogenesis; Phosphatase; Phosphatases; Proteins; RNA, Messenger; Roles; Spondylitis, Ankylosing - genetics; Substrates; T cell receptors; T-Lymphocytes; Threonine; Tumor necrosis factor; Tumor Necrosis Factor-alpha; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Tyrosine; γ-Interferon; United States; New York; United States > US; Germany; DUSP22; Tumor necrosis factor-α; Interleukin-17A; Interferon-γ; Ankylosing spondylitis
• ISSN: 1741-7015; 1741-7015
• DOI: 10.1186/s12916-023-02745-6

Dual-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). Sixty 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. The 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. DUSP22 may play a crucial role in the pathogenesis and regulation of disease activity of AS.