DUSP23 is over‐expressed and linked to the expression of DNMTs in CD4+ T cells from systemic lupus erythematosus patients

• Published in: Clinical and experimental immunology 2017-02, Vol.187 (2), p.242-250
• Main Authors: Balada, E., Felip, L., Ordi‐Ros, J., Vilardell‐Tarrés, M.
• Format: Article
• Language: English
• Subjects: Adult; CD11a Antigen - metabolism; CD4-Positive T-Lymphocytes - immunology; CD40 Ligand - metabolism; Cells, Cultured; DNA Methylation; DNA Modification Methylases - genetics; DNA Modification Methylases - metabolism; DNMTs, DUSP23; Dual-Specificity Phosphatases - genetics; Dual-Specificity Phosphatases - metabolism; epigenetics; Female; Humans; lupus; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Male; Middle Aged; Original; Perforin - metabolism; Young Adult
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/cei.12883

Summary We evaluated the transcriptional expression of dual‐specificity protein phosphatase 23 (DUSP23) in CD4+ T cells from 30 systemic lupus erythematosus (SLE) patients and 30 healthy controls. DUSP23 mRNA levels were considerably higher in the patient group: 1490 ± 1713 versus 294·1 ± 204·2. No association was found between DUSP23 mRNA expression and the presence of typical serological and clinical parameters associated with SLE. Meaningful statistical values were obtained in the patient group between the levels of DUSP23 and integrin subunit alpha L (ITGAL), perforin 1 (PRF1) and CD40L. Similarly, transcript levels of different DNA methylation‐related enzymes [DNA methylation‐related enzymes (DNMT1, DNMT3A, DNMT3B, MBD2, and MBD4)] were also correlated positively with the expression of DUSP23. In an attempt to counteract the hypomethylation status of the promoters of certain genes known to be over‐expressed in SLE, it is possible that DUSP23 acts as a negative regulatory mechanism which ultimately silences the transcription of these epigenetically regulated genes by triggering an increase in the expression of different DNMTs. We have determined the transcription levels of DUSP23 in SLE patients. These levels are increased and they correlate with the levels of different DNMTs, potentially leading to the assumption that DUSP23 may act as a regulatory mechanism to silence some of the genes overexpressed in SLE, such as ITGAL, PRF1 and CD40L.