Similar Datasets
Project description:Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by systemic inflammation that involves various immune cell types. Monocytes are central players in promoting and regulating inflammation. Different monocyte subsets exist and change their proportions during physiological immune responses and under pathological conditions, including SLE, supporting different roles in inflammatory responses. In this study, we obtained the epigenetic and transcriptomic profiles of the three monocyte subsets, classical, intermediate and non-classical monocytes in an SLE cohort. We found different common and subset-specific alterations. While SLE classical monocytes had a stronger proinflammatory profile with an important interferon influence priming them towards macrophage differentiation, non-classical monocytes had a phenotype related to T cell differentiation regulation, with several indications pointing towards a Th17 promoting behavior. Integration of these bulk datasets with single-cell RNA-seq data of an SLE cohort shed light on the heterogeneity of our monocytes, confirming the interferon signature profile of classical monocytes and pointing towards intermediate and non-classical populations associated with exacerbated complement activation pathways, among others. With this analysis, we confirm the differential role of monocyte subsets in the pathogenesis of SLE and give insight into their regulatory mechanisms.
2024-10-30 | GSE249639 | GEO
Project description:Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by systemic inflammation that involves various immune cell types. Monocytes play a central role in promoting and regulating inflammation. Peripheral blood classical monocytes subsequently differentiate into intermediate monocytes and then non-classical monocytes, assuming diverse roles and undergoing changes in their proportions during physiological immune responses and pathological conditions, including SLE. In this study, we obtained the epigenetic and transcriptomic profiles of these three monocyte subsets in an SLE cohort. We found different common and subset-specific alterations. While SLE classical monocytes had a stronger proinflammatory profile with an important interferon influence priming them towards macrophage differentiation, non-classical monocytes had a phenotype related to T cell differentiation regulation, with several indications pointing towards a Th17 promoting behavior. Integration of these bulk datasets with single-cell RNA-seq data of an SLE cohort shed light on the heterogeneity of our monocytes, confirming the interferon signature profile of classical monocytes and pointing towards intermediate and non-classical populations associated with exacerbated complement activation pathways, among others. Our results indicate a subversion of the epigenome and transcriptome in monocyte differentiation toward non-classical subsets in SLE, involving the STAT1 pathway and impacting function in relation to disease activity.
2024-10-30 | GSE249619 | GEO
Project description:Divergent Epigenetic and Transcriptomic Remodelling during Monocyte Subset Differentiation in Systemic Lupus Erythematosus
| PRJNA1049862 | ENA
Project description:Divergent Epigenetic and Transcriptomic Remodelling during Monocyte Subset Differentiation in Systemic Lupus Erythematosus [methylation]
| PRJNA1049861 | ENA
Project description:Divergent Epigenetic and Transcriptomic Remodelling during Monocyte Subset Differentiation in Systemic Lupus Erythematosus [RNA-seq]
| PRJNA1049831 | ENA
Project description:Autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, multiple sclerosis, autoimmune hepatitis, and inflammatory bowel disease have complex pathogeneses and the courses of events leading to these diseases are not well understood. The immune surveillance is a delicate balance between self and foreign as well as between tolerance and immune response. Exposure to certain environmental factors may impair this equilibrium, leading to autoimmune diseases, cancer, and the so-called "lifestyle diseases" such as atherosclerosis, heart attack, stroke, and obesity, among others. These external stimuli may also alter the epigenetic status quo and may trigger autoimmune diseases such as SLE in genetically susceptible individuals. This review aims to highlight the role of epigenetic (dys-)regulation in the pathogenesis of SLE.
| S-EPMC4883254 | biostudies-literature
Project description:TLR7/8 and TLR9 signaling pathways have been extensively studied in systemic lupus erythematosus (SLE) as possible mediators of disease. Monocytes are a major source of pro-inflammatory cytokines and are understudied in SLE. In the current project, we investigated sex differences in monocyte activation and its implications in SLE disease pathogenesis.Human blood samples from 27 healthy male controls, 32 healthy female controls, and 25 female patients with SLE matched for age and race were studied. Monocyte activation was tested by flow cytometry and ELISA, including subset proportions, CD14, CD80 and CD86 expression, the percentage of IL-6-producing monocytes, plasma levels of sCD14 and IL-6, and urine levels of creatinine.Monocytes were significantly more activated in women compared to men and in patients with SLE compared to controls in vivo. We observed increased proportions of non-classic monocytes, decreased proportions of classic monocytes, elevated levels of plasma sCD14 as well as reduced surface expression of CD14 on monocytes comparing women to men and lupus patients to controls. Plasma levels of IL-6 were positively related to sCD14 and serum creatinine.Monocyte activation and TLR4 responsiveness are altered in women compared to men and in patients with SLE compared to controls. These sex differences may allow persistent systemic inflammation and resultant enhanced SLE susceptibility.
| S-EPMC4259347 | biostudies-other
Project description:ObjectiveHistone modifications set transcriptional competency and can perpetuate pathologic expression patterns. We defined systemic lupus erythematosus (SLE)-specific changes in H3K4me3 and K3K27me3, histone marks of gene activation and repression, respectively.MethodsWe used ChIP-seq to define histone modifications in monocytes from SLE patients and controls.ResultsBoth promoters and enhancers exhibited significant changes in histone methylation in SLE. Regions with differential H3K4me3 in SLE were significantly enriched in potential interferon-related transcription factor binding sites and pioneer transcription factor sites.ConclusionEnhancer activation defines the character of the cell and our data support extensive disease effects in monocytes, a particularly plastic lineage. Type I interferons not only drive altered gene expression but may also alter the character of the cell through chromatin modifications.
| S-EPMC4864065 | biostudies-literature
Project description:Neutrophil dysregulation is implicated in the pathogenesis of systemic lupus erythematosus (SLE). SLE is characterized by elevated levels of a pathogenic neutrophil subset known as low-density granulocytes (LDGs). The origin and phenotypic, functional, and pathogenic heterogeneity of LDGs remain to be systematically determined. Transcriptomics and epigenetic assessment of lupus LDGs, autologous normal-density neutrophils, and healthy control neutrophils was performed by bulk and single-cell RNA sequencing and assay for transposase-accessible chromatin sequencing. Functional readouts were compared among neutrophil subsets. SLE LDGs display significant transcriptional and epigenetic heterogeneity and comprise 2 subpopulations of intermediate-mature and immature neutrophils, with different degrees of chromatin accessibility and differences in transcription factor motif analysis. Differences in neutrophil extracellular trap (NET) formation, oxidized mitochondrial DNA release, chemotaxis, phagocytosis, degranulation, ability to harm the endothelium, and responses to type I interferon (IFN) stimulation are evident among LDG subsets. Compared with other immune cell subsets, LDGs display the highest expression of IFN-inducible genes. Distinct LDG subsets correlate with specific clinical features of lupus and with the presence and severity of coronary artery disease. Phenotypic, functional, and pathogenic neutrophil heterogeneity are prevalent in SLE and may promote immune dysregulation and prominent vascular damage characteristic of this disease.
| S-EPMC6911190 | biostudies-literature
Project description:The pathogenesis of systemic lupus erythematosus (SLE) is influenced by both genetic factors and epigenetic modifications; the latter is a result of exposure to various environmental factors. Epigenetic modifications affect gene expression and alter cellular functions without modifying the genomic sequences. CpG-DNA methylation, histone modifications, and miRNAs are the main epigenetic factors of gene regulation. In SLE, global and gene-specific DNA methylation changes have been demonstrated to occur in CD4+ T-cells. Moreover, histone acetylation and deacetylation inhibitors reverse the expression of multiple genes involved in SLE, indicating histone modification in SLE. Autoreactive T-cells and B-cells have been shown to alter the patterns of epigenetic changes in SLE patients. Understanding the molecular mechanisms involved in the pathogenesis of SLE is critical for the introduction of effective, target-directed and tolerated therapies. In this review, we summarize the recent findings that highlight the importance of epigenetic modifications and their mechanisms in SLE.
| S-EPMC6058186 | biostudies-literature