Dual-specificity phosphatases 22-deficient T cells contribute to the pathogenesis of ankylosing spondylitis. 2023

Ming-Han Chen, and Huai-Chia Chuang, and Yi-Chen Yeh, and Chung-Tei Chou, and Tse-Hua Tan
Division of Allergy, Immunology & Rheumatology, Taipei Veterans General Hospital, Taipei, Taiwan.

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.

UI MeSH Term Description Entries
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D013167 Spondylitis, Ankylosing A chronic inflammatory condition affecting the axial joints, such as the SACROILIAC JOINT and other intervertebral or costovertebral joints. It occurs predominantly in young males and is characterized by pain and stiffness of joints (ANKYLOSIS) with inflammation at tendon insertions. Ankylosing Spondylitis,Bechterew Disease,Marie-Struempell Disease,Rheumatoid Spondylitis,Spondylarthritis Ankylopoietica,Ankylosing Spondylarthritis,Ankylosing Spondyloarthritis,Bechterew's Disease,Spondylitis Ankylopoietica,Spondyloarthritis Ankylopoietica,Ankylosing Spondylarthritides,Ankylosing Spondyloarthritides,Bechterews Disease,Marie Struempell Disease,Spondylarthritides, Ankylosing,Spondylarthritis, Ankylosing,Spondylitis, Rheumatoid,Spondyloarthritides, Ankylosing,Spondyloarthritis, Ankylosing
D013601 T-Lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D014409 Tumor Necrosis Factor-alpha Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS. Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D054637 Dual-Specificity Phosphatases A sub-class of protein tyrosine phosphatases that contain an additional phosphatase activity which cleaves phosphate ester bonds on SERINE or THREONINE residues that are located on the same protein. DUSP Phosphatases,Dual-Specificity Phosphatase,Dual Specificity Phosphatase,Dual Specificity Phosphatases,Phosphatase, Dual-Specificity,Phosphatases, DUSP,Phosphatases, Dual-Specificity
D018345 Mice, Knockout Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes. Knockout Mice,Mice, Knock-out,Mouse, Knockout,Knock-out Mice,Knockout Mouse,Mice, Knock out

Related Publications

Ming-Han Chen, and Huai-Chia Chuang, and Yi-Chen Yeh, and Chung-Tei Chou, and Tse-Hua Tan
January 2015, Experimental and therapeutic medicine,
Ming-Han Chen, and Huai-Chia Chuang, and Yi-Chen Yeh, and Chung-Tei Chou, and Tse-Hua Tan
April 1979, Annals of the rheumatic diseases,
Ming-Han Chen, and Huai-Chia Chuang, and Yi-Chen Yeh, and Chung-Tei Chou, and Tse-Hua Tan
June 1975, Annals of clinical research,
Ming-Han Chen, and Huai-Chia Chuang, and Yi-Chen Yeh, and Chung-Tei Chou, and Tse-Hua Tan
January 2008, Neurosurgical focus,
Ming-Han Chen, and Huai-Chia Chuang, and Yi-Chen Yeh, and Chung-Tei Chou, and Tse-Hua Tan
July 2010, Nature reviews. Rheumatology,
Ming-Han Chen, and Huai-Chia Chuang, and Yi-Chen Yeh, and Chung-Tei Chou, and Tse-Hua Tan
April 2018, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie,
Ming-Han Chen, and Huai-Chia Chuang, and Yi-Chen Yeh, and Chung-Tei Chou, and Tse-Hua Tan
January 2018, Clinical immunology (Orlando, Fla.),
Ming-Han Chen, and Huai-Chia Chuang, and Yi-Chen Yeh, and Chung-Tei Chou, and Tse-Hua Tan
March 1981, Fortschritte der Medizin,
Ming-Han Chen, and Huai-Chia Chuang, and Yi-Chen Yeh, and Chung-Tei Chou, and Tse-Hua Tan
February 2001, Chinese medical journal,
Ming-Han Chen, and Huai-Chia Chuang, and Yi-Chen Yeh, and Chung-Tei Chou, and Tse-Hua Tan
June 2016, Clinical rheumatology,
Copied contents to your clipboard!