Erratum: Roles of 1,25(OH)<sub>2</sub>D<sub>3</sub> and Vitamin D Receptor in the Pathogenesis of Rheumatoid Arthritis and Systemic Lupus Erythematosus by Regulating the Activation of CD4<sup>+</sup> T Cells and the PKCδ/ERK Signaling Pathway

<b><i>Background/Aims: </i></b>The study aims to elucidate the roles of 1,25(OH)<sub>2</sub>D<sub>3</sub> and vitamin D receptor (VDR) in the pathogenesis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) by regulating the activation of CD4<sup>+</sup> T cells and the PKCδ/ERK signaling pathway. <b><i>Methods:</i></b> From January 2013 to December 2015, a total of 130 SLE patients, 137 RA patients and 130 healthy controls were selected in this study. Serum levels of 1,25(OH)<sub>2</sub>D<sub>3</sub> and VDR mRNA expression were detected by ELISA and real-time fluorescence quantitative PCR (RT-qPCR). Density gradient centrifugation was performed to separate peripheral blood mononuclear cells (PBMCs). CD4<sup>+</sup> T cells were separated using magnetic activated cell sorting (MACS). CD4<sup>+</sup>T cells in logarithmic growth phase were collected and assigned into 9 groups: the normal control group, the normal negative control (NC) group, the VDR siRNA group, the RA control group, the RA NC group, the VDR over-expressed RA group, the SLE control group, the SLE NC group, and the VDR over-expressed SLE group. The mRNA and protein expressions of VDR, PKCδ, ERK1/2, CD11a, CD70 and CD40L were detected by RT-qPCR and Western blotting. Bisulfite genomic sequencing was conducted to monitor the methylation status of CD11a, CD70 and CD40L. <b><i>Results:</i></b> Compared with healthy controls, serum 1,25(OH)<sub>2</sub>D<sub>3</sub> level and VDR mRNA expression in peripheral blood were decreased in SLE patients and RA patients. With the increase of concentrations of 1,25(OH)<sub>2</sub>D<sub>3</sub> treatment, the VDR mRNA expression and DNA methylation levels of CD11a, CD70 and CD40L were declined, while the expressions of PKCδ, ERK1/2, CD11a, CD70 and CD40L were elevated in SLE, RA and normal CD4<sup>+</sup>T cells. Compared with the SLE contro, RA control, SLE NC and RA NC groups, the expressions of PKCδ, ERK1/2, CD11a, CD70 and CD40L decreased but DNA methylation levels of CD11a, CD70 and CD40L increased in the VDR over-expressed SLE group and VDR over-expressed RA group. However, compared with the normal control and normal NC groups, the expressions of PKCδ, ERK1/2, CD11a, CD70 and CD40L increased, but DNA methylation levels of CD11a, CD70 and CD40L decreased in the VDR siRNA group. Compared with the normal control group, the expressions of PKCδ, ERK1/2, CD11a, CD70 and CD40L increased, but DNA methylation levels of CD11a, CD70 and CD40L decreased in the SLE control and RA control groups. <b><i>Conclusion: </i></b>Our study provide evidence that 1,25(OH)<sub>2</sub>D<sub>3</sub> and VDR could inhibit the activation of CD4<sup>+</sup> T cells and suppress the immune response of SLE and RA through inhibiting PKCδ/ERK pathway and promoting DNA methylation of CD11a, CD70 and CD40L.