Overexpression of OASL upregulates TET1 to induce aberrant activation of CD4(+) T cells in systemic sclerosis via IRF1 signaling

BACKGROUND: Systemic sclerosis (SSc), an autoimmune disease with unknown etiology and pathogenesis, is characterized by abnormal autoimmunity, vascular dysfunction, and progressive fibrosis of skin and organs. Studies have shown that a key factor in the pathogenesis of SSc is aberrant activation of CD4(+) T cells. Our previous studies have shown that a global hypomethylation state of CD4(+) T cells is closely related to aberrant activation. However, the exact mechanism of hypomethylation in CD4+T cells is not yet clear. METHODS: Illumina HiSeq 2500 Platform was used to screen differentially expressed genes and explore the role of OASL, TET1, and IRF1 in the abnormal activation of CD4+T cells in SSc. Finally, double luciferase reporter gene experiments were used to analyze the interaction between IRF1 and TET1. RESULTS: OASL overexpression could upregulate TET1 to increase the hydroxymethylation levels of CD4+ T cells and induce high expression of functional proteins (CD40L and CD70), thus promoting CD4+T cell aberrant activation. Moreover, OASL upregulated TET1 via IRF1 signaling activation, and a double luciferase reporter gene experiment revealed that IRF1 can bind to the TET1 promoter region to regulate its expression. CONCLUSIONS: OASL participates in the regulation of abnormal hypomethylation of CD4+ T cells in SSc, which implies a pivotal role for IFN signaling in the pathogenesis of SSc. Regulating DNA methylation and IFN signaling may serve as therapeutic treatments in SSc. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-022-02741-w.