Intra-ocular dendritic cells characterize HLA-B27-associated acute anterior uveitis
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ABSTRACT:
PROVIDER: PRJNA741216 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
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| SRR14904525.fastq.gz | Fastqsanger.gz | |||
| SRR14904526.fastq.gz | Fastqsanger.gz | |||
| SRR14904527.fastq.gz | Fastqsanger.gz | |||
| SRR14904528.fastq.gz | Fastqsanger.gz | |||
| SRR14904529.fastq.gz | Fastqsanger.gz |
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Project description:Uveitis describes a heterogeneous group of inflammatory eye diseases characterized by infiltration of leukocytes into the uveal tissues. uveitis associated with the HLA haplotype B27 (HLA-B27) is a common subtype of uveitis and a prototypical ocular immune-mediated disease. Local immune mechanisms driving human uveitis are poorly characterized mainly due to the limited available biomaterial and subsequent technical limitations. Here, we provide the first high-resolution characterization of intraocular leukocytes in HLA-B27 positive (n=3) and negative (n=2) anterior uveitis and an infectious endophthalmitis control (n=1) by combining single cell RNA-sequencing with flow cytometry and protein analysis. Ocular cell infiltrates consisted primarily of lymphocytes in both subtypes of uveitis and of myeloid cells in infectious endophthalmitis. HLA-B27 positive uveitis exclusively featured a plasmacytoid and classical dendritic cells (cDC) infiltrate. Moreover, cDCs were central in predicted local cell-cell communication. This suggests a unique pattern of ocular leukocyte infiltration in HLA-B27 positive uveitis with relevance of dendritic cells.
2021-06-25 | GSE178833 | GEO
Project description:HLA-B27-associated inflammatory diseases remains one of the strongest HLA-disease known to date. HLA-B27-associated acute anterior uveitis has wide-ranging medical significance due to its ocular, systemic, immunologic, and genetic features. To investigate the genes and signalling pathways located upstream of the inflammatory processes in HLA-B27-associated acute anterior uveitis will help to know the mechanism of this disease. HLA-B27-positive and -negative monocytes isolated from human peripheral blood were stimulated with Vibrio cholera lipopolysaccharide (LPS). Gene expression microarrays were used to identify the differentially expressed genes, and they were analysed by a series of bioinformatics-based techniques. Gene expression microarray analysis revealed marked differences between B27-positive monocytes in the genes that are upregulated in response to LPS stimulation. Gene Ontology enrichment (GO) and pathway analysis indicated that genes participating in protein transport and folding were essential to the inflammatory process. The LPS receptor, TLR4, induced the Toll-like receptor signalling pathway and pathways related to Vibrio cholerae infection, which are located upstream of the network and contribute to the overall response. Among the DE genes, PIK3CA, PIK3CB, AKT3, and MAPK1 may play critical roles in inflammation.Equivalent LPS stimulation induces a different response in HLA-B27-positive monocytes compared to monocytes lacking this HLA protein, suggesting that the TLR pathway is involved in the pathogenesis of HLA-B27-associated AAU. Blocking this pathway and other pathways by siRNA interference of candidate genes may contribute to the development of a treatment for this type of AAU. HLA-B27-positive monocytes isolated from human peripheral blood were stimulated with Vibrio cholera lipopolysaccharide (LPS) for 12 hours.
2012-05-31 | E-GEOD-37588 | biostudies-arrayexpress
Project description:HLA-B27-associated inflammatory diseases remains one of the strongest HLA-disease known to date. HLA-B27-associated acute anterior uveitis has wide-ranging medical significance due to its ocular, systemic, immunologic, and genetic features. To investigate the genes and signalling pathways located upstream of the inflammatory processes in HLA-B27-associated acute anterior uveitis will help to know the mechanism of this disease. HLA-B27-positive and -negative monocytes isolated from human peripheral blood were stimulated with Vibrio cholera lipopolysaccharide (LPS). Gene expression microarrays were used to identify the differentially expressed genes, and they were analysed by a series of bioinformatics-based techniques. Gene expression microarray analysis revealed marked differences between B27-positive monocytes in the genes that are upregulated in response to LPS stimulation. Gene Ontology enrichment (GO) and pathway analysis indicated that genes participating in protein transport and folding were essential to the inflammatory process. The LPS receptor, TLR4, induced the Toll-like receptor signalling pathway and pathways related to Vibrio cholerae infection, which are located upstream of the network and contribute to the overall response. Among the DE genes, PIK3CA, PIK3CB, AKT3, and MAPK1 may play critical roles in inflammation.Equivalent LPS stimulation induces a different response in HLA-B27-positive monocytes compared to monocytes lacking this HLA protein, suggesting that the TLR pathway is involved in the pathogenesis of HLA-B27-associated AAU. Blocking this pathway and other pathways by siRNA interference of candidate genes may contribute to the development of a treatment for this type of AAU.
2012-06-01 | GSE37588 | GEO
Project description:Associations of the Intestinal Microbiome and HLA-B27-associated anterior uveitis
| PRJEB55787 | ENA
Project description:Uveitis describes a heterogeneous group of inflammatory eye diseases characterized by infiltration of leukocytes into the uveal tissues. Uveitis associated with the HLA haplotype B27 (HLA-B27) is a common subtype of uveitis and a prototypical ocular immune-mediated disease. Local immune mechanisms driving human uveitis are poorly characterized mainly due to the limited available biomaterial and subsequent technical limitations. Here, we provide the first high-resolution characterization of intraocular leukocytes in HLA-B27-positive (n = 4) and -negative (n = 2) anterior uveitis and an infectious endophthalmitis control (n = 1) by combining single-cell RNA-sequencing with flow cytometry and protein analysis. Ocular cell infiltrates consisted primarily of lymphocytes in both subtypes of uveitis and of myeloid cells in infectious endophthalmitis. HLA-B27-positive uveitis exclusively featured a plasmacytoid and classical dendritic cell (cDC) infiltrate. Moreover, cDCs were central in predicted local cell-cell communication. This suggests a unique pattern of ocular leukocyte infiltration in HLA-B27-positive uveitis with relevance to DCs.
| S-EPMC8594918 | biostudies-literature
Project description:Uveitis is characterised by breakdown of the blood-retinal barrier (BRB), allowing infiltration of immune cells that mediate intraocular inflammation, which can lead to irreversible damage of the neuroretina and the loss of sight. Treatment of uveitis relies heavily on corticosteroids and systemic immunosuppression due to limited understanding of the molecular immune interactions that underpin ocular immune homeostasis. By performing single-cell transcriptomic analysis of whole dissociated mouse retinas with experimental autoimmune uveitis (EAU) versus healthy control, we gained an unbiased appreciation of the immune interactions that drive retinal inflammation in a model of posterior uveitis.
2024-08-29 | GSE241700 | GEO
Project description:Uveitis is an immune-inflammatory disease that can cause blindness. However, little is known about a comprehensive atlas of the ocular cellular and inflammatory components in uveitis. Here, single-cell RNA sequencing was performed to construct a transcriptomic atlas of ocular cells from experimental autoimmune uveitis (EAU) and control mice to identify disease- associated immune cell subsets and molecules. We reveal 15 cell types in eyes and found an α-Synuclein positive microglia subset and plasma cell subset with high level of cytokines. The heterogeneous plasma cells subsets communicated with DC, T cells and retinal cells via various cytokines and molecular pairing. The G protein Rab1A participated in the inflammatory response of plasma cells. Altogether, we revealed the heterogeneous inflammatory genes, EAU-specific immune cell populations, and dysregulated communications of immune and retinal cells in EAU. This result provides a systematic view of the transcriptional map of uveitis and a foundation for studying the cellular and molecular mechanisms and pathogenesis of this disease.
2023-07-10 | GSE236389 | GEO
Project description:Objectives How HLA-B27 contributes towards arthritis susceptibility is still unclear, but effects on the response to bacteria unrelated to the classical antigen presenting role of B27 have been suggested. This study investigated whether HLA-B27 modulates the innate response to LPS, a component shared between all Gram –ve bacteria that can trigger reactive arthritis. Methods Pools of U937 transfectants expressing either HLA-B27, HLA-A2, or the expression plasmid alone were differentiated with PMA and stimulated with LPS. Supernatants were analysed for TNF-alpha secretion and the gene expression profiles of unstimulated and LPS stimulated cells were determined by microarray analysis. Changes in gene expression that are indicative of an unfolded protein response were also analysed by quantitative PCR. Results TNF-alpha secretion, a biological marker of the inflammatory response to LPS, was not significantly different between U937-B27 and U937-control. No differences in gene expression between unstimulated U937- B27 and U937-control lines were detected. Both U937-control and U937-B27 exhibited a stereotypic response to LPS. Only 1 gene, OAS2, was differentially expressed by these cell lines, and this was confirmed by quantitative PCR. Analysis of XBP-1 splicing suggested that a small increase in the unfolded protein response is induced following LPS stimulation, but this increase was seen in all transfectants. Conclusions The expression of B27 does not profoundly alter gene expression following LPS stimulation. Therefore, additional signals, such as those provided by cytokines or intracellular infection, may be required to reveal any influence of B27 expression on the inflammatory response. Keywords: antigen response
2006-04-10 | GSE4579 | GEO
Project description:The discovery of the association of HLA B27 with spondyloarthropathy led to more questions than answers about the role of this gene in disease susceptibility. The realization that HLA B27 was not responsible for all of the genetic effects helped to lay a foundation for further investigation into the genetics of uveitis. Over several decades, genetic findings have provided clues to advance the understanding of mechanisms of uveitis and to catalyze new research on diagnostics, animal models, and therapies. From the early candidate gene studies on immune mediators to the recent genome-wide investigations, much has been discovered. However, these discoveries have come with the caveat that a genetic finding does not automatically reveal the disease-relevant functional effect of the associated variant.
| S-EPMC3083239 | biostudies-literature
Project description:PurposeTo evaluate choroidal changes in eyes with acute anterior uveitis associated with human leukocyte antigen (HLA)-B27.MethodsIn 44 patients with first-onset, unilateral, acute-onset (<1 week) anterior uveitis for which diagnostic work-ups revealed positivity only for HLA-B27, wide-field three-dimensional volumetric raster scan using swept-source optical coherence tomography was performed for both eyes. Choroidal thickness was measured by automated segmentation and thickness mapping and compared between eyes with uveitis and the fellow eyes at baseline. Choroidal thickness was compared before and after topical and/or systemic corticosteroid therapy. Relative choroidal thickening was defined as the choroidal thickness of the uveitic eye minus that of the corresponding eye and correlated with the degree of intraocular inflammation.ResultsCompared to the fellow eyes, eyes with acute anterior uveitis showed significant choroidal thickening on the subfoveal and parafoveal areas at baseline (all P <0.05). En face choroidal imaging showed dilation of large choroidal vessels on the macula. Relative choroidal thickening significantly correlated with the degree of anterior chamber inflammation at baseline (correlation coefficient = 0.341, P = 0.023). After treating inflammation, the choroid on the macula thinned significantly (from 262.1 ± 66.5 to 239.5 ± 61.0 μm in the subfoveal choroid, P<0.001).ConclusionsEyes with HLA-B27-associated anterior uveitis showed significant choroidal thickening at acute phase that subsequently decreased after treatment, indicating subclinical choroidal inflammation in the eyes. Choroidal thickness might indicate disease activity in acute anterior uveitis associated with HLA-B27.
| S-EPMC5489203 | biostudies-literature