IL-6/STAT3 pathway induced deficiency of RFX1 contributes to Th17-dependent autoimmune diseases via epigenetic regulation.

Epigenetic modifications affect the differentiation of T cell subsets and the pathogenesis of autoimmune diseases, but many mechanisms of epigenetic regulation of T cell differentiation are unclear. Here we show reduced expression of the transcription factor RFX1 in CD4 T cells from patients with systemic lupus erythematosus, which leads to IL-17A overexpression through increased histone H3 acetylation and decreased DNA methylation and H3K9 tri-methylation. Conditional deletion of Rfx1 in mice exacerbates experimental autoimmune encephalomyelitis and pristane-induced lupus-like syndrome and increases induction of Th17 cells.

Distinct epigenomes in CD4 T cells of newborns, middle-ages and centenarians.

Age-related variations in genes and microRNAs expression and DNA methylation have been reported respectively; however, their interactions during aging are unclear. We therefore investigated alterations in the transcriptomes, miRNAomes and DNA methylomes in the same CD4T cells from newborn (NB), middle-aged (MA) and long-lived (LL) individuals to elucidate the molecular changes and their interactions. A total 659 genes showed significantly expression changes across NB, MA and LL individuals, in which we identified four age-related co-expression modules with three hub networks of co-expressed genes and non-coding RNAs.

The effect of mycophenolic acid on epigenetic modifications in lupus CD4+T cells.

Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease involving multiple organs and characterized by overproduction of autoantibodies and T and B cell abnormalities. The treatment for SLE has been restricted to immunosuppressants and corticosteroids. Mycophenolate mofetil (MMF), as a relatively new immunosuppressant, is now widely used in the treatment of SLE patients, particularly those with nephritis.

The role of microRNA-1246 in the regulation of B cell activation and the pathogenesis of systemic lupus erythematosus.

Background: The pathogenesis of systemic lupus erythematosus (SLE) has not yet been completely elucidated. One of the hallmarks of SLE is the production of autoantibodies by uncontrolled over-activated B cells. Early B cell factor 1 (EBF1) contributes to the development, activation, and proliferation of B cells through activation of the AKT signaling pathway.

Peripheral whole blood FOXP3 TSDR methylation: a potential marker in severity assessment of autoimmune diseases and chronic infections.

Immune dysregulation is a cardinal feature of autoimmune diseases and chronic microbial infections. In particular, regulatory T cells are downregulated in autoimmune diseases while upregulated in chronic microbial infections. FOXP3 is the master regulator of Treg development.

A possible role of HMGB1 in DNA demethylation in CD4+ T cells from patients with systemic lupus erythematosus.

The aberrant activity of CD4(+) T cells in patients with systemic lupus erythematosus (SLE) is associated with DNA hypomethylation of the regulatory regions in CD11a and CD70 genes. Our previous studies demonstrated that Gadd45a contributes to the development of SLE by promoting DNA demethylation in CD4(+) T cells. In this study, we identified proteins that bind to Gadd45a in CD4(+) T cells during SLE flare by using the method of co-immunoprecipitation and mass spectrometry, High mobility group box protein 1 (HMGB1) is one of identified proteins.

[DNA methylation status of miR-126 and its host gene EGFL7 in CD4+ T cells from patients with systemic lupus erythematosus].

Objective: To explore the mechanisms by which DNA methylation regulates miR-126 and its host gene EGFL7 in CD4+ T cells from patients with systemic lupus erythematosus (SLE).

Methods: We analyzed the expression and the DNA methylation status within promoter region of EGFL7 and miR-126 by real-time qPCR and bisulfite genomic sequencing analysis.

Results: miR-126 and EGFL7 mRNA expression was upregulated in CD4+ T cells from SLE compared with that from healthy controls (P<0.

Aberrant histone modification in peripheral blood B cells from patients with systemic sclerosis.

Objectives: To investigate alterations in histone modifications in B cells and their role in the pathogenesis of systemic sclerosis (SSc).

Methods: Global histone H3/H4 acetylation and H3K4/H3K9 methylation in B cells of SSc were tested by EpiQuik™ assay kits. Related histone modifier enzymes were measured by RT-PCR and Western blot.

[Construction of special reporter to detect DNA methylation regulatory activity in FCER1G gene promoter through patch-methylation].

Objective: To construct a special luciferase reporter to detect DNA methylation regulatory activity in FCER1G gene promoter regulatory element.

Methods: We constructed special full and mock methylated FCER1G gene promoter regulatory luciferase reporters by patch-methylation, and detected DNA methylation regulatory activity by comparing the luciferase activity of full-methylated luciferase reporters with mock-methylated reporters.

Results: We successfully constructed the full and mock methylated FCER1G gene promoter regulatory luciferase reporters.

Whole-genome DNA methylation in skin lesions from patients with psoriasis vulgaris.

Psoriasis, a chronic inflammatory skin disorder, is characterized by aberrant keratinocyte proliferation and differentiation in the epidermis. Although the pathogenesis of psoriasis is still incompletely understood, both genetic susceptibilities and environmental triggers are known to act as key players in its development. Several studies have suggested that DNA methylation is involved in the pathogenesis of psoriasis.

Aberrant histone modifications in peripheral blood mononuclear cells from patients with Henoch-Schönlein purpura.

Henoch-Schönlein purpura (HSP), the most common type of leukocytoclastic vasculitis, is caused by T cell-mediated autoimmune reactions. In this study, we analyze histone modification patterns in peripheral blood mononuclear cells (PBMCs) of HSP patients, and investigate the expression levels of inflammatory cytokines (IFN-γ, IL-2, IL-4, IL-6 and IL-13), transcription factors (T-bet, GATA-3 and TIM-1) and chemokines (CXCL4 and CXCL10) in HSP patients. Our results show that histone H3 acetylation and methylation are significantly enhanced in PBMCs from HSP patients.

E4BP4 overexpression: a protective mechanism in CD4+ T cells from SLE patients.

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease characterized by various immunological abnormalities, including dysregulated activation of T and B lymphocytes, which trigger autoantibody production and immune-complex deposition. E4BP4, also known as NFIL3, has emerged as a major transcription factor that regulates the development and function of immune cells in a number of lineages. E4BP4 has been shown to regulate cytokines expression, and its synthesis is in turn controlled by various cytokines.

[Effect of total glucosides of peony on expression and DNA methylation status of ITGAL gene in CD4(+) T cells of systemic lupus erythematosus].

Objective: To investigate the effect of total glucosides of peony (TGP) on expression and DNA methylation status of ITGAL gene (CD11a) in CD4(+) T cells from patients with systemic lupus erythematosus (SLE).

Methods: CD4(+) T cells were isolated by positive selection using CD4 beads. CD4(+) T cells were treated by TGP at 0, 62.

Decreased microRNA-142-3p/5p expression causes CD4+ T cell activation and B cell hyperstimulation in systemic lupus erythematosus.

Objective: To examine the role of microRNA-142-3p/5p (miR-142-3p/5p) in the development of autoimmunity in patients with systemic lupus erythematosus (SLE).

Methods: MicroRNA-142-3p/5p expression levels were determined by real-time quantitative polymerase chain reaction, and potential target genes were verified using luciferase reporter gene assays. The effects of miR-142-3p/5p on T cell function were assessed by transfection with miR-142-3p/5p inhibitors or mimics.

Total glucosides of paeony induces regulatory CD4(+)CD25(+) T cells by increasing Foxp3 demethylation in lupus CD4(+) T cells.

Total glucosides of paeony (TGP), an active compound extracted from Paeony root, has been used in therapy for autoimmune diseases. However the molecular mechanism of TGP in the prevention of autoimmune response remains unclear. In this study, we found that TGP treatment significantly increased the percentage and number of Treg cells in lupus CD4(+) T cells.

Inhibited expression of hematopoietic progenitor kinase 1 associated with loss of jumonji domain containing 3 promoter binding contributes to autoimmunity in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by T cell overactivation and B cell hyper-stimulation. Hematopoietic progenitor kinase 1 (HPK1, also called MAP4K1) negatively regulates T cell-mediated immune responses. However, the role of HPK1 and the mechanisms that regulate HPK1 expression in SLE remain poorly understood.

Abnormal DNA methylation in CD4+ T cells from people with latent autoimmune diabetes in adults.

Aberrant DNA methylation in T cells has been linked to pathogenesis of autoimmune diseases. To investigate genomic and gene-specific DNA methylation levels in CD4(+) T cells from patients with latent autoimmune diabetes in adults (LADA), and to investigate changes in the expression of genes that regulate methylation as well as the autoimmune-related gene FOXP3 in these patients. Global CD4(+) T cell DNA methylation was measured in 15 LADA patients and 11 healthy controls using a methylation quantification kit.

RFX1 regulates CD70 and CD11a expression in lupus T cells by recruiting the histone methyltransferase SUV39H1.

Introduction: Regulatory factor X-box 1 (RFX1) can interact with DNA methyltransferase 1 (DNMT1) and histone deacetylase 1 (HDAC1), and RFX1 down-regulation contributes to DNA hypomethylation and histone H3 hyperacetylation at the cluster of differentiation (CD) 11a and CD70 promoters in CD4(+) T cells of patients with systemic lupus erythematosus (SLE). This leads to CD11a and CD70 overexpression, thereby triggering autoimmune responses. In order to provide more insight into the epigenetic mechanisms leading to the deregulation of autoimmune-related genes in SLE, we asked whether RFX1 is involved in regulating histone 3 lysine 9 (H3K9) tri-methylation at the CD11a and CD70 promoters in SLE CD4(+) T cells.