Dataset Information

Promotion of Treg/Th17 Balance in MRL/lpr Mice by Jianpi-Zishen Formula Via Modulation of DNMT1-Mediated Foxp3 Methylation

ABSTRACT: A total of 48 female MRL/lpr mice were included in this study and divided into six groups: JPZS group (Low, medium, and high doses), 5-aza-CdR group, and DC_517 group, with eight mice in each group. Eight female C57BL/6 mice were used as controls. The mice were subjected to the corresponding intervention measures for eight weeks. The impact of JPZS on the disease progression of MRL/lpr mice was evaluated using enzyme-linked immunosorbent assay (ELISA) and serum biochemical parameters. Moreover, immunofluorescence staining and flow cytometry were employed to investigate alterations in the proportions of Tregs and Th17 cells. CD4+ T cells were isolated from the spleen for subsequent investigation, including quantitative real-time PCR, western blotting, and determination of DNA methylation levels. Furthermore, the enzymatic activity of CD4+ T cell-specific DNA methyltransferases was quantified using an EpiQuik DNMT detection kit.The results indicate that JPZS significantly improved the disease development of MRL/lpr mice in a dose-dependent manner. Immunofluorescence staining and flow cytometry suggest that JPZS can increase the ratio of Treg/Th17. Research has found that Foxp3 is at a high methylation level in CD4+ T cells of the model group, and the transcription level of Foxp3 mRNA is downregulated; JPZS can downregulate Foxp3 methylation levels of CD4+ T cells in the model group. Further research has found that the level of Foxp3 methylation is closely related to Dnmt1 enzyme activity, and JPZS can downregulate Dnmt1 enzyme activity, thereby upregulating the transcription level of Foxp3 mRNA.

ORGANISM(S): Mus musculus

PROVIDER: GSE296851 | GEO | 2025/05/31

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Our previous study demonstrated a significant upregulation of a large set of miRNAs at the genomic imprinted Dlk1-Dio3 locus in lymphocytes of diverse murine lupus-prone strains. The upregulation of Dlk1-Dio3 miRNAs in lupus-prone mice is correlated with the global DNA hypomethylation. In this study, by performing genome-wide DNA methylation analysis, we reported that Dlk1-Dio3 genomic region in CD4+ T cells of MRL/lpr mice was hypomethylated, further linking hypomethylation to the increased expression of Dlk1-Dio3 miRNAs in lupus. Then, we assessed the gene expression levels of enzymes that either write (DNA methyltransferases, DNMTs) or erase DNA methylation (Ten-eleven translation proteins, TETs) to understand the molecular contributor to the DNA hypomethylation in MRL/lpr CD4+ T cells. The expression levels of Dnmt1, Dnmt3b, Tet1, and Tet2 were significantly increased in CD4+ T cells of MRL/lpr mice, as well as in B6/lpr and B6.sle123 mice, compared to their respective control mice. These data indicate the significant involvement of the TETs-mediated active demethylation pathway rather than reduced DNMTs-mediated passive demethylation pathway in the hypomethylation of murine lupus CD4+ T cells. The transcription factor, early growth response 2 (EGR2) is critically involved in regulating T cell functions and autoimmunity. In this research, we found that Egr2 deletion in B6/lpr mice notably reduced methylation-sensitive Dlk1-Dio3 cluster miRNAs expression in CD4+ T cells. Surprisingly, even though EGR2 has been shown to induce DNA demethylation by recruiting TET2, we found that deleting Egr2 in B6/lpr mice induced a higher number of hypomethylated DMRs than hypermethylated DMRs at either whole genome or the Dlk1-Dio3 locus in CD4+ T cells of B6/lpr mice. These data are the first finding on the positive role of EGR2 on the expression of Dlk1-Dio3 cluster miRNAs in lupus mice. Given that Dlk1-Dio3 miRNAs target the major signaling pathways in autoimmunity, these data provide a new perspective in understanding the potential pathogenic role of upregulated EGR2 in lupus.

Dataset Information

Promotion of Treg/Th17 Balance in MRL/lpr Mice by Jianpi-Zishen Formula Via Modulation of DNMT1-Mediated Foxp3 Methylation

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets