Dual-Specificity Phosphatases 22-Deficient T Cells Contribute to the Pathogenesis of Ankylosing Spondylitis

Authors

Ming-Han Chen
Huai-Chia Chuang
Yi-Chen Yeh
Chung-Tei Chou
Tse-Hua Tan

Language

English

Publication Date

2-10-2023

Journal

BMC Medicine

DOI

10.1186/s12916-023-02745-6

PMID

36765305

PMCID

PMC9921195

PubMedCentral® Posted Date

2-10-2023

PubMedCentral® Full Text Version

Post-print

Abstract

Background: 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).

Methods: 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.

Results: 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.

Conclusions: DUSP22 may play a crucial role in the pathogenesis and regulation of disease activity of AS.

Keywords: Ankylosing spondylitis; DUSP22; Int

Keywords

Animals, Mice, Dual-Specificity Phosphatases, Mice, Knockout, RNA, Messenger, Spondylitis, Ankylosing, T-Lymphocytes, Tumor Necrosis Factor-alpha, DUSP22, Ankylosing spondylitis, Tumor necrosis factor-α, Interferon-γ, Interleukin-17A

Published Open-Access

yes

Recommended Citation

Chen, Ming-Han; Chuang, Huai-Chia; Yeh, Yi-Chen; et al., "Dual-Specificity Phosphatases 22-Deficient T Cells Contribute to the Pathogenesis of Ankylosing Spondylitis" (2023). Children’s Nutrition Research Center Staff Publications. 247.
https://digitalcommons.library.tmc.edu/staff_pub/247