Acute atopic dermatitis and urticaria imprints peripheral monocytes with proinflammatory-prone signature
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE255396 | GEO | 2024/02/28
REPOSITORIES: GEO
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Project description:Monocytes from patients with type 2 immune disorders exhibited an augmented inflammatory response upon LPS stimulation. RNA-seq analysis demonstrated significant upregulation of inflammatory cytokines, including IL-6, IL-12, and IL-1b. Moreover, there was a conspicuous enrichment of signaling pathways associated with inflammation. ATAC sequencing revealed heightened chromatin accessibility in patient monocytes, particularly in the promoter regions of inflammatory genes.
2024-07-01 | GSE256444 | GEO
Project description:Acute atopic dermatitis and urticaria imprints peripheral monocytes with proinflammatory-prone signature
| PRJNA1074805 | ENA
Project description:Acute atopic dermatitis and urticaria imprints peripheral monocytes with proinflammatory-prone signature
| PRJNA1079688 | ENA
Project description:Background: Atopic dermatitis (AD) is a common inflammatory skin disease with broad impact on quality of life and on the health care system. The pathophysiology is not fully understood, but it is likely multifactorial involving immune dysfunction, altered skin barrier and environmental factors. Narrow band ultraviolet B (nb-UVB) treatment leads to normalization of the tissue and clinical improvement. However, knowledge of early changes in AD skin in response to nb-UVB is lacking and could provide important clues to decipher the disease mechanisms and potential new treatment targets. Objective: To map the early transcriptional changes in the skin in response to nb-UVB treatment. Results: When examining the early response after only three local UVB-treatments, gene expression analysis revealed 30 down- and 47 up-regulated transcripts. Among these only a small proportion were related to the inflammatory response. Interestingly, two cytokines of the interleukin (IL)-1 family were differentially expressed: the proinflammatory cytokine IL-36γ was reduced after treatment, while the anti-inflammatory cytokine IL-37 increased in skin after treatment with nb-UVB. Conclusion: Local nb-UVB induced an early decrease of the pro-inflammatory cytokine IL-36γ and an increase of the anti-inflammatory IL-37. This likely represents one of the first changes in inflammatory signaling induced by nb-UVB in atopic eczema.
2020-10-27 | GSE150797 | GEO
Project description:BackgroundMonitoring the effects of biologic therapies in skin diseases will benefit from alternative noninvasive skin sampling techniques to evaluate immune pathways in diseased tissue early and longitudinally.ObjectiveTo establish a minimally invasive profiling of skin cytokines for diagnosis, therapeutic response monitoring, and clinical research in atopic dermatitis (AD) and other skin diseases, particularly in pediatric cohorts.MethodsWe developed a novel method for cytokine profiling in the epidermis using skin tape strips (STSs) in a setting designed to maximize the efficiency of protein extraction from STSs. This method was applied to analyze STS protein extracts from the lesional skin of children having AD (n = 41) and normal, healthy controls (n = 22). A total of 20 cytokines were probed with the ultrasensitive Mesoscale multiplex cytokine assay.ResultsA significant increase in interleukin (IL)-1b (P < .01), IL-18 (P < .001), and IL-8 (P < .001) with a decrease in IL-1a (P < .001) in the stratum corneum of AD lesional skin was found. Concurrently, an increase in markers associated with type 2 inflammatory response was readily detectable in AD lesional skin, including C-C motif chemokine ligand (CCL) 22, CCL 17, and thymic stromal lymphopoietin (TSLP). The levels of IL-1b, IL-18, and TSLP exhibited positive correlations with the AD severity index (Scoring AD index) and skin transepidermal water loss (TEWL), whereas an inverse correlation between IL-1a and Scoring AD index and IL-1a and TEWL was found. The levels of CCL17, CCL22, TSLP, IL-22, and IL-17a correlated with skin TEWL measurements.ConclusionUsing minimally invasive STS analysis, we identified cytokine profiles easily sampled in AD lesional skin. The expression of these markers correlated with disease severity and reflected changes in TEWL in lesional skin. These markers suggest new response assessment targets for AD skin.Trial registrationClinicalTrials.gov Identifier: NCT03168113.
| S-EPMC8782053 | biostudies-literature
Project description:Atopic Dermatitis (AD) is the most common inflammatory skin disease and characterized by a deficient epidermal barrier and cutaneous inflammation. Genetic studies suggest a key role of keratinocytes in AD pathogenesis, but the alterations in the proteome that occur in the entire epidermis have not been defined. Employing a pressure-cycling technology-data-independent acquisition (PCT-DIA) approach, we performed quantitative proteomics of epidermis from healthy volunteers and lesional and non-lesional skin of AD patients. Results were validated by targeted proteomics using parallel reaction monitoring mass spectrometry or by immunofluorescence staining. The identified proteins reflect the strong inflammation in lesional skin and the defect in keratinocyte differentiation and epidermal stratification. Most importantly, they reveal impaired activation of the NRF2-antioxidant pathway and reduced abundance of mitochondrial proteins involved in key metabolic pathways in the epidermis. These results provide insight into the molecular alterations in the epidermis of AD patients and identify novel targets for pharmaceutical intervention.
2022-10-04 | PXD025431 | Pride
Project description:BackgroundLife-threatening viral diseases such as eczema herpeticum (EH) and eczema vaccinatum (EV) occur in <5% of individuals with atopic dermatitis (AD). The diagnosis of AD, however, excludes all individuals with AD from smallpox vaccination.ObjectivesWe sought to identify circulatory and skin lipid biomarkers associated with EH and EV.MethodsStratum corneum and plasma samples from 15 subjects with AD and a history of EH, 13 age- and gender-matched subjects with AD and without EH history, and 13 healthy nonatopic (NA) controls were analyzed by liquid chromatography tandem mass spectrometry for sphingolipid content. Sphingosine-1-phosphate (S1P) and ceramide levels were validated in plasma samples from the Atopic Dermatitis Vaccinia Network/Atopic Dermatitis Research Network repository (12 NA, 12 AD, 23 EH) and plasma from 7 subjects with EV and 7 matched subjects with AD. S1P lyase was downregulated in human primary keratinocytes to evaluate its effect on herpes simplex virus 1 (HSV-1) replication in vitro.ResultsThe stratum corneum of patients with EH demonstrated significantly higher levels of free sphingoid bases than those in patients who were NA, indicating enhanced sphingolipid turnover in keratinocytes (P < .05). Plasma from 2 independent cohorts of patients with EH had a significantly increased S1P/ceramide ratio in subjects with EH versus those with AD and or who were NA (P < .01). The S1P level in plasma from subjects with EV was twice the level in plasma from subjects with AD (mean = 1,533 vs 732 pmol/mL; P < .001). Downregulation of S1P lyase expression with silencing RNA led to an increased S1P level and doubled HSV-1 titer in keratinocytes.ConclusionsOur data point to long-term abnormalities in the S1P signaling system as a biomarker for previous disseminated viral diseases and a potential treatment target in recurring infections.
| S-EPMC9463085 | biostudies-literature
Project description:Insight into the pathophysiology of inflammatory skin diseases, especially at the proteomic level, is severely hampered by the lack of adequate in situ data. Skin microdialysis samples from patients with atopic dermatitis (AD, n=6), psoriasis vulgaris (PSO, n=7) or prurigo nodularis (PN, n=6), as well as healthy controls (n=7) were subjected to proteomics and multiplex cytokine analysis. Single-cell RNA sequencing of skin biopsy specimens was used to identify the cellular origin of cytokines. Among the top 20 enriched GO annotations, NAD metabolic process, regulation of secretion by cell, and pyruvate metabolic process were elevated in microdialysates from lesional AD skin compared with both nonlesional skin and controls. The top 20 enriched KEGG pathways in these three groups overlapped almost completely. In contrast, nonlesional skin from patients with PSO or PN and control skin showed no overlap with lesional skin in this KEGG pathway analysis. Lesional skin from patients with PSO, but not AD or PN, showed significantly elevated protein levels of IL-22 and MCP-1 compared to nonlesional skin. IL-8 was elevated in lesional vs nonlesional AD and PSO skin, whereas IL-12p40 was higher only in lesional PSO skin. Integrated single-cell RNA-seq data revealed identical cellular sources of these cytokines in AD, PSO and PN. Based on microdialysate, proteomic data of lesional PSO and PN skin, but not lesional AD skin, differed significantly from those of nonlesional skin. IL-8, IL-22, MCP-1 and IL-12p40 might be suitable markers for minimally invasive molecular profiling.
2024-08-22 | PXD050245 | Pride
Project description:Background: Atopic dermatitis (AD) is a common inflammatory skin disease with a TH2 immune polarity and is often colonized with Staphylococcus aureus. Despite recent advances in understanding Staphylococcus species infection and the impact of polar TH cytokines on the skin, the interactions between these factors in AD pathology are poorly understood. Methods: AD-related key immune biomarkers were measured by quantitative real-time PCR in human keratinocytes exposed heat-killed S. epidermidis or S. aureus with/without polar T-cell derived cytokines such as IFN-γ (TH1), IL-4/IL-13 (TH2), and IL-22 (TH22). Further analysis was performed by RNA-sequencing to define broader responses in both Staphylococcus species and polar cytokines. The similarity of gene expression patterns in AD skin lesions and stimulated keratinocytes was evaluated by gene-set variation analysis (GSVA). Results: Gene expression analysis exhibited distinct immune responses in keratinocytes depending on individual bacterial or polar cytokine exposure. Besides, numerous genes were synergistically upregulated by the combination exposure of bacteria and polar TH cytokines. Moreover, GSVA revealed that combined exposure of S. aureus and IL-4 + IL-13 exhibited significantly higher correlations with a genomic signature of AD skin lesions than their single exposure or combinations of other polar TH cytokines. Conclusions: Our findings provide novel insights into AD-related transcriptional activation and illustrate a potentially novel pathogenic function of S. aureus and IL-4/IL-13 interactions in AD.
2021-12-31 | GSE173902 | GEO
Project description:COVID-19 patients are generally asymptomatic during initial SARS-CoV-2 replication, but may suffer severe immunopathology after the virus has receded and blood monocytes have infiltrated the airways. In the bronchoalveolar lavage fluid from patients with severe COVID-19, lung-infiltrating monocytes expressed high mRNA levels encoding inflammatory mediators, including CXCL8and IL-1ß, and contained SARS-CoV-2transcripts. To study this process in more depth, we developed a novel organotypic model whereby primary human blood monocytes are transmigrated across a differentiated human lung epithelium infected by SARS-CoV-2. Infiltrating monocytes acquiredSARS-CoV-2 from the epithelium and upregulated expression and secretion of inflammatory mediators includingCXCL8 and IL-1ß, mirroring in vivo data. The JAK1/2inhibitor baricitinib gained emergency use authorization by the FDA for the treatment of COVID-19 originally in combination with the antiviral remdesivir, and recently as a stand-alone treatment. To explore the mechanisms by which baricitinib alone or in combination with remdesivir may result in more favorable disease outcomes, we leveraged this model to characterize viral burden, gene expression and inflammatory mediator secretion by lung epithelial cells and infiltrating monocytes. As expected, remdesivir decreased viral burden in both the epithelium and monocytes, while baricitinib enhanced antiviral signaling and decreased specific inflammatory mediators in monocytes. Combined use of baricitinib and remdesivir enhanced the rate of virus clearance from SARS-CoV-2-positivemonocytes. Taken together, baricitinib enhances the antiviral state of monocytes infiltrating the COVID-19 lung, while decreasing the expression of inflammatory mediators, thus limiting the likelihood of a cytokine storm and ensuing acute respiratory distress syndrome (ARDS).
2021-10-30 | GSE186460 | GEO