Single-cell transcriptomics reveals peripheral immune responses in non-segmental vitiligo
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ABSTRACT:
SUBMITTER: Yang P
PROVIDER: S-EPMC10702986 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:Vitiligo is a common autoimmune depigmented dermatology due to the destruction of melanocytes. Much evidence suggests that vitiligo is associated with systemic immune activation. Previous studies have focused on immune cell infiltration in and around lesion areas, while few studies have investigated the cell types and function of circulating immune cells in peripheral blood. We collected peripheral blood from five patients with progressive non-segmental vitiligo (PV) and three healthy controls (HC).Single-cell RNA sequencing(scRNA-seq) is used to investigate the mechanisms of peripheral immune responses in vitiligo patients.
2023-11-07 | GSE231794 | GEO
Project description:Single-Cell Transcriptomics Reveals Peripheral Immune Responses in Non-Segmental Vitiligo
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Project description:This study integrates single-cell RNA and ATAC sequencing to profile peripheral immune cells in nonsegmental vitiligo, providing insights into systemic immune dysregulation.
2025-02-05 | GSE282793 | GEO
Project description:ObjectiveInterstitial lung diseases (ILDs) secondary to anti-synthetase syndrome (ASS) greatly influence the prognoses of patients with ASS. Here we aimed to investigate the peripheral immune responses to understand the pathogenesis of this condition.MethodsWe performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from 5 patients with ASS-ILD and 3 healthy donors (HDs). Flow cytometry of PBMCs was performed to replenish the results of scRNA-seq.ResultsWe used scRNA-seq to depict a high-resolution visualization of cellular landscape in PBMCs from patients with ASS-ILD. Patients showed upregulated interferon responses among NK cells, monocytes, T cells, and B cells. And the ratio of effector memory CD8 T cells to naïve CD8 T cells was significantly higher in patients than that in HDs. Additionally, Th1, Th2, and Th17 cell differentiation signaling pathways were enriched in T cells. Flow cytometry analyses showed increased proportions of Th17 cells and Th2 cells, and decreased proportion of Th1 cells in patients with ASS-ILD when compared with HDs, evaluated by the expression patterns of chemokine receptors.ConclusionsThe scRNA-seq data analyses reveal that ASS-ILD is characterized by upregulated interferon responses, altered CD8 T cell homeostasis, and involvement of differentiation signaling pathways of CD4 T cells. The flow cytometry analyses show that the proportions of Th17 cells and Th2 cells are increased and the proportion of Th1 cells is decreased in patients with ASS-ILD. These findings may provide foundations of novel therapeutic targets for patients with this condition.
| S-EPMC8891123 | biostudies-literature
Project description:Immune cells and immune microenvironment play important in the evolution of sepsis. This study aimed to explore hub genes related to the abundance of immune cell infiltration in sepsis. The GEOquery package is used to download and organize data from the GEO database. A total of 61 differentially expressed genes (DEGs) between sepsis samples and normal samples were obtained through the 'limma' package. T cells, natural killer (NK) cells, monocytes, megakaryocytes, dendritic cells (DCs), and B cells formed six distinct clusters on the t-distributed stochastic neighbor embedding (t-SNE) plot generated using the Seurat R package. Gene set enrichment analysis (GSEA) enrichment analysis showed that sepsis samples and normal samples were related to Neutrophil Degranulation, Modulators of Tcr Signaling and T Cell Activation, IL 17 Pathway, T Cell Receptor Signaling Pathway, Ctl Pathway, Immunoregulatory Interactions Between a Lymphoid and A Non-Lymphoid Cell. GO analysis and KEGG analysis of immune-related genes showed that the intersection genes were mainly associated with Immune-related signaling pathways. Seven hub genes (CD28, CD3D, CD2, CD4, IL7R, LCK, and CD3E) were screened using Maximal Clique Centrality, Maximum neighborhood component, and Density of Maximum Neighborhood Component algorithms. The lower expression of the six hub genes (CD28, CD3D, CD4, IL7R, LCK, and CD3E) was observed in sepsis samples. We observed the significant difference of several immune cell between sepsis samples and control samples. Finally, we carried out in vivo animal experiments, including Western blotting, flow cytometry, Elisa, and qPCR assays to detect the concentration and the expression of several immune factors.
| S-EPMC10126435 | biostudies-literature
Project description:ObjectiveWe explored the patterns of long non-coding RNA (lncRNA) expression in peripheral blood mononuclear cells (PBMCs) from patients with non-segmental vitiligo.MethodsWe used high-throughput RNA sequencing technology to generate sequence data from five patients with non-segmental vitiligo alongside five normal healthy individuals, and then performed bioinformatics analyses to detect the differential expression of lncRNA in PBMCs. Gene Ontology (GO) and pathway analyses were performed for functional annotation, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify gene expression. Target miRNAs and mRNAs of differentially expressed lncRNAs were predicted using bioinformatics analysis.ResultsA total of 292 lncRNAs were differentially expressed in non-segmental vitiligo (fold change ≥ 2.0, P < .05), of which 171 were upregulated and 121 were downregulated. Six differentially expressed lncRNAs were selected, namely ENST00000460164.1, ENST00000393264.2, NR-046211.1, NR-135491.1, NR-135320.1, and ENST00000381108.3, for validation by qRT-PCR. The results showed that ENST00000460164.1 and NR-046211.1 were highly expressed in PBMCs of non-segmental vitiligo. An lncRNA-miRNA-mRNA network containing two lncRNAs, 17 miRNAs, and 223 mRNAs was constructed.ConclusionOur results revealed patterns of differentially expressed lncRNAs in the PBMCs of non-segmental vitiligo individuals. ENST00000460164.1, and NR-046211.1 may be potential biomarkers and drug targets for the treatment of non-segmental vitiligo.
| S-EPMC8702240 | biostudies-literature
Project description: Not available
| S-EPMC10951445 | biostudies-literature
Project description:Comprehensive Single-Cell Chromatin and Transcriptomic Profiling of Peripheral Immune Cells in Non-Segmental Vitiligo
| PRJNA1190435 | ENA
Project description:Cellular senescence is induced in response to cellular stressors such as increased levels of reactive oxygen species. The chronic accumulation of senescent cells is currently recognized as a contributor to the pathologic processes of diverse degenerative diseases. Vitiligo is characterized by the disappearance of melanocytes driven by cellular stress within melanocytes and autoimmune processes. In this study, we examined p16INK4A positivity in the lesional and perilesional skin of 54 non-segmental vitiligo patients to explore cellular senescence in vitiligo. There were more p16INK4A-positive melanocytes in the perilesional vitiligo skin samples than in control samples. It was also found that p16INK4A immunoreactivity was not restricted to melanocytes but also existed in fibroblasts; the number of p16INK4A-positive fibroblasts was significantly increased in lesional skin compared to perilesional skin and normal controls. However, in the subgroup analysis of sun-exposed and non-exposed samples, this outcome was only found at sun-exposed sites, suggesting that fibroblast senescence is an epiphenomenon related to the loss of pigment in skin with vitiligo. In summary, exploring p16INK4A positivity in vitiligo revealed melanocyte senescence in perilesional skin, which may play a role in vitiligo pathogenesis.
| S-EPMC7694005 | biostudies-literature
Project description:BackgroundMyasthenia gravis (MG) is the most prevalent autoimmune disorder affecting the neuromuscular junction. A rapid deterioration in respiratory muscle can lead to a myasthenic crisis (MC), which represents a life-threatening condition with high mortality in MG. Multiple CD4+ T subsets and hypercytokinemia have been identified in the peripheral pro-inflammatory milieu during the crisis. However, the pathogenesis is complicated due to the many types of cells involved, leaving the underlying mechanism largely unexplored.MethodsWe conducted single-cell transcriptomic and immune repertoire sequencing on 33,577 peripheral blood mononuclear cells (PBMCs) from two acetylcholine receptor antibody-positive (AChR +) MG patients during MC and again three months post-MC. We followed the Scanpy workflow for quality control, dimension reduction, and clustering of the single-cell data. Subsequently, we annotated high-resolution cell types utilizing transfer-learning models derived from publicly available single-cell immune datasets. RNA velocity calculations from unspliced and spliced mRNAs were applied to infer cellular state progression. We analyzed cell communication and MG-relevant cytokines and chemokines to identify potential inflammation initiators.ResultsWe identified a unique subset of monocytes, termed monocytes 3 (FCGR3B+ monocytes), which exhibited significant differential expression of pro-inflammatory signaling pathways during and after the crisis. In line with the activated innate immune state indicated by MC, a high neutrophil-lymphocyte ratio (NLR) was confirmed in an additional 22 AChR + MC patients in subsequent hemogram analysis and was associated with MG-relevant clinical scores. Furthermore, oligoclonal expansions were identified in age-associated B cells exhibiting high autoimmune activity, and in CD4+ and CD8+ T cells demonstrating persistent T exhaustion.ConclusionsIn summary, our integrated analysis of single-cell transcriptomics and TCR/BCR sequencing has underscored the role of innate immune activation which is associated with hypercytokinemia in MC. The identification of a specific monocyte cluster that dominates the peripheral immune profile may provide some hints into the etiology and pathology of MC. However, future functional studies are required to explore causality.
| S-EPMC10464341 | biostudies-literature