Monocytes as endogenous immunologic biosensors: identification of inflammatory, adhesion, and mTOR-related signatures in psoriasis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE161906 | GEO | 2021/03/30
REPOSITORIES: GEO
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Project description:Topical dithranol (anthralin) has remained an effective anti-psoriatic agent. Although dithranol has been used for many years, it has never been fully revealed how dithranol exerts its anti-psoriatic mechanisms.Thus, we studied the therapeutic mechanisms of this drug in serial biopsies from human psoriatic lesions.
2024-03-06 | GSE249936 | GEO
Project description:Monocytes as endogenous immunologic biosensors: identification of inflammatory, adhesion, and mTOR-related signatures in psoriasis
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Project description:Psoriasis is a common inflammatory skin disease with complex etiology and chronic progression. To provide novel insights into the molecular mechanisms of regulation of the disease we performed RNA sequencing (RNA-Seq) analysis of fourteen pairs of skin samples collected from psoriatic patients with consequent pathway analysis and identification of the main transcriptional regulators of psoriasis-associated pathways. In order to identify the most important regulators of the disease, we combined the results obtained with MetaCore Interactome enrichment tool and cisExpress algorithm and compared them to regulatory psoriasis response elements found in literature. Comparative approach allowed us to identify 42 core transcriptional regulators of the disease associated with inflammation (NFkB, IRF9, JUN, FOS, SRF), activity of T-cells in the psoriatic lesions (STAT6, FOXP3, NFATC2, GATA3, TCF7, RUNX1, etc.), hyper-proliferation and migration of keratinocytes (JUN, FOS, NFIB, TFAP2A, TFAP2C), and with lipid metabolism (TFAP2, RARA, VDR). We also identified 66 transcription factors not previously associated with psoriasis. Using MetaCore pathway maps we illustrated and described the molecular basis of psoriatic skin lesions.
2017-09-14 | GSE78023 | GEO
Project description:To understand immunological differences between recurred and non-recurred psoriatic lesion after cease of treatment with ixekizumab
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Project description:Psoriasis patients exhibit an increased risk of death by cardiovascular disease (CVD) and have elevated levels of circulating intermediate (CD14++CD16+) monocytes. This elevation could represent evidence of monocyte dysfunction in psoriasis patients at risk of CVD, as increases in circulating CD14++CD16+ monocytes are predictive of myocardial infarction and death. An elevation in the CD14++CD16+ cell population has been previously reported in patients with psoriatic disease, which has been confirmed in the cohort of our human psoriasis patients. CD16 expression was induced in CD14++CD16neg classical monocytes following plastic adhesion, which also elicited enhanced β2 but not β1 integrin surface expression, suggesting increased adhesive capacity. Indeed, we found that psoriasis patients have increased monocyte aggregation among circulating PBMCs which is recapitulated in the KC-Tie2 murine model of psoriasis. Visualization of human monocyte aggregates using imaging cytometry revealed that classical CD14++CD16neg monocytes are the predominant cell type participating in these aggregate pairs. Many of these pairs also included CD16+ monocytes, which could account for apparent elevations of intermediate monocytes. Additionally, intermediate monocytes and monocyte aggregates were the predominant cell type to adhere to TNF-α and IL-17A-stimulated dermal endothelium. Ingenuity Pathway Analysis (IPA) demonstrated that monocyte aggregates have a distinct transcriptional profile from singlet monocytes and monocytes following plastic adhesion, suggesting that circulating monocyte responses to aggregation are not fully accounted for by homotypic adhesion, and that further factors influence their functionality. qRT-PCR Gene Expression Profiling - 30 Samples Analyzed, 10 biological replicates, 10 Control Samples, 20 Test Samples
2015-06-27 | E-GEOD-70327 | biostudies-arrayexpress
Project description:Object: To study the difference of gene expression pattern of bone marrow mesenchymal stem cells (BMMSCs) between psoriatic patients, normal adults and aborted fetuses, and then to explore the influence of bone marrow mesenchymal stem cells to immune system. Methods: Bone marrow mononuclear cells (BMMNC) of 7 psoriatic patients, 4 healthy volunteers and 3 aborted fetuses were isolated and the BMMSCs were cultured using the adherent method. Gene expression of 14 samples was detected by gene microarray and the different expressed genes were analysised by SAM software. Results: 654 differentially expressed genes (66 up regulated, 588 down regulated) were detected between the psoriatic patients and normal adults, which were enriched in immune response, chemotaxis and cell adhesion etc. 2020 differentially expressed genes (888 up regulated, 1132 down regulated) were detected between the aborted fetuses and normal adults. These genes were enriched in cell cycle, cell division, immune response and MHC class II antigen etc. Conclusion: The gene expression pattern such as immune response, chemotaxis was aberrant in psoriatic BMMNCs, which was consistent with aborted fetuses in some immune related genes. Bone marrow mononuclear cells (BMMNC) of 7 psoriatic patients, 4 healthy volunteers and 3 aborted fetuses were isolated and the BMMSCs were cultured using the adherent method. Gene expression of 14 samples was detected by gene microarray and the different expressed genes were analyzed by SAM software.
2012-08-10 | E-GEOD-40033 | biostudies-arrayexpress
Project description:Monocytes play a critical role in the inflammation associated with psoriasis, and their abnormalities have been reported as biomarkers of cardiovascular event risk, a psoriasis comorbidity. Monocytic cells in chronic inflammatory disorders express elevated levels of cAMP phosphodiesterase. Restoring cAMP levels using the oral cAMP phosphodiesterase-4 inhibitor, apremilast, improves clinical outcomes for a subset of psoriasis patients. We asked whether aberrant monocyte subsets or transcriptomic pathways can function as biomarkers of psoriasis endotypes that can predict enhanced clinical responses to cAMP phosphodiesterase inhibition. A 16-week open-label study of 22 patients with monocyte flow cytometric and transcriptomic analysis was performed. Subjects with elevated hyper-adhesive monocyte doublets at baseline were more likely to be responders to apremilast (p< 0.0001); 82% of subjects with elevated hyper-adhesive monocyte doublets achieved 50% reduction in PASI (PASI50) compared to 46% in those without elevated doublets. We observed a significant reduction in hyper-adhesive monocyte-containing doublets and monocyte-platelet aggregates, suggesting an effect of apremilast on the adhesiveness of blood monocytes during chronic inflammation. Monocyte differentially-expressed gene transcripts predictive of clinical response uncovered pharmaco-endotypes with distinct patterns of nucleotide metabolism, energetics, and differentiation. Further study to understand the basis of drug responsiveness, and to develop an apremilast psoriasis treatment algorithm using monocyte refined gene expression is required to validate and become practical in clinical use, offering patients a test that personalizes their likelihood of clinical response.
2024-02-26 | GSE256275 | GEO
Project description:To further explore the gene expression signatures in psoriatic, we have employed whole genome microarray expression profiling as a discovery platform to identify the potential genes that play a role in the pathogenesis of psoriasis. 3 psoriasis specimens were collected from patients with psoriasis and 3 normal skin were obtained from cosmetic surgeries as controls.The analysis identified a set of 4956 differentially expressed circRNAs，2194 significantly dysregulated lncRNAs，and 1725 discrepant mRNAs .Among all the differential expressed circRNAs, 3016 upregulated circRNAs and 1940 downregulated circRNAs were found in psoriatic lesions compared with normal healthy skin tissues.
2021-08-03 | GSE181318 | GEO
Project description:Comparison of gene expression profiles of mast cells isolated from lesional psoriatic and healthy volunteer skin
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Project description:Several studies have suggested that MSCs have pleiotropic immuno-modulatory effects, including inhibition of T cell proliferation, suppression of NK cells proliferation, modulation of cytokine production, and inhibition of dendritic cell (DC) maturation etc. But the exactly mechanism are still largely unclear.We have found that the gene expression profile of psoriatic dermal MSCs was distinct different from normal MSCs. We proposed to investigate the DNA methylation profile of psoriatic MSCs. 6 patients and 6 normal control were inrolled in the study, the DNA methylation profile of dermal MSCs were studied using the microarry.
2012-11-30 | E-GEOD-42634 | biostudies-arrayexpress