Project description:Systemic lupus erythematosus is a relapsing autoimmune disease that affects multiple organ systems. T cells play an important role in the pathogenesis of lupus, however, early T cell events triggering disease flares are incompletely understood. We studied DNA methylation in naïve CD4+ T cells from lupus patients to determine if epigenetic landscape change in CD4+ T cells is an early event in lupus flares.
Project description:ATAC-seq analysis of CD4 T cell populations obtained in blood of systemic lupus erythematosus (SLE) patients. The overall goal of this study was to determine chromatin accessibility profiles in Tfh cells and CXCR3+ PD1hi CD4+ T cells obtained from blood of SLE donors.
Project description:Mature double negative (DN) T cells are αβ T cells lacking CD4/CD8 coreceptors and expanded in patients with systemic lupus erythematosus (SLE). It is not known whether they display a narrow or expander TCR repertoire.
Project description:Male patients with systemic lupus erythematosus (SLE) experience severe disease compared to female patients, despite the disease being more prevalent in females. For the time, we compared genome-wide differential methylation in CD4+ T cells between male (n=12) and female (n=10) SLE patients.
Project description:To investigate the lncRNAs expression profiling in CD4+ T cells of systemic lupus erythematosus (SLE) patients, we have employed “Agilent Human lncRNA 4*180K microarray” as a discovery platform to identify lncRNAs and mRNAs expression signatures in CD4+ T cells between SLE patients and normal controls. CD4+ T cells were isolated from peripheral blood mononuclear cells (PBMCs) of peripheral blood in SLE patients and normal controls, respectively.
Project description:Foxp3+ regulatory T cells (Treg), playing a crucial role in the maintenance of immune tolerance and prevention of autoimmune diseases, consist of thymus-derived naturally-occurring CD4+Foxp3+ Treg cells (nTreg) and another CD4+Foxp3+ Treg cells that can be induced ex vivo with TGF-β (iTreg). Although both Treg subsets share similar phenotypes and functional characteristics, they also have potential biologic differences on their biology. However, the role of iTreg in regulating B cells of lupus disease mice remains unclear so far. The lupus-prone New Zealand Mixed 2328 (NZM2328) mouse, a recombinant inbred strain that originated from the crosses among New Zealand Black and New Zealand White mice and their progenies also develops Lupus Glomerulonephritis. NZM2328 mice develop autoantibodies and glomerulonephritis with female predominance similarly to humans with systemic lupus erythematosus. The lupus disease onset is usually around 3-4 months age. In our experiments, iTreg induced from NZM2328 lupus-prone mice (10-12 weeks old) and nTreg sorted from the thymus of 10-12 weeks old NZM2328 lupus-prone mice were adoptively transferred into old NZM2328 mice (>4 months age) with established lupus for 32 days. Totally, there were three groups including NZM2328 mice as model (receive PBS), NZM2328 mice received iTreg, and NZM2328 received nTreg. The serum IgG and IgM autoantibody were detected by autoantibodies microarrays (UTSW Medical Center Autoantigen Array) at days 0, 14, 32 after cell transfer. Our results demonstrated that adoptive transfer of iTreg had a superior effect than nTreg subset on suppressing lupus B cell responses in vivo.
Project description:T-cells are important in the pathogenesis of juvenile-onset systemic lupus erythematosus (JSLE). Transcriptomic analysis of FACS sorted primary CD4+ and CD8+ T-cells was performed to assess differential gene expression in patient groups.
Project description:Systemic lupus erythematosus (SLE) is a chronic-relapsing autoimmune disease of incompletely understood etiology. Recent evidence strongly supports an epigenetic contribution to the pathogenesis of lupus. To understand the extent and nature of dysregulated DNA methylation in lupus T cells, we performed a genome-wide DNA methylation study in CD4+ T cells from 12 lupus patients and 12 normal healthy controls. Cytosine methylation was quantified in 27,578 CG pairs located within the promoter regions of 14,495 genes. We identified 236 hypomethylated and 105 hypermethylated CG sites in lupus CD4+ T cells compared to normal controls, consistent with a global hypomethylation in lupus T cells. Further analysis identified hypomethylation in genes involved in connective tissue development including CD9, MMP9, and PDGFRA. Hypermethylated genes highlight “response to nutrients” ontology such as folate biosynthesis, suggesting a link between environmental factor and lupus and emphasizing the role of folate in DNA methylation. In addition, the transcription factor RUNX3 was hypermethylated in lupus CD4+ T cells. Protein-protein interaction maps identified a transcription factor, HNF4a, as a regulatory hub affecting a number of differentially methylated genes. Functional annotations such as apoptosis is also overrepresented. Further, our data indicate that the methylation status of certain genes predicts disease activity in lupus patients. This work provides a foundation to begin identifying novel pathogenic pathways in lupus T cells and developing novel epigenetic biomarkers for disease activity in lupus. We employed microarray-based technologies to perform a genome-wide DNA methylation assay and quantify CD4+ T cell DNA methylation levels at 27,578 CG sites spanning 14,495 genes of 11 lupus patients and 12 healthy controls.
