Spontaneously resolved atopic dermatitis shows melanocyte and immune cell activation distinct from healthy control skin
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ABSTRACT:
PROVIDER: PRJNA680371 | ENA |
REPOSITORIES: ENA
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Project description:Atopic dermatitis (AD) typically starts in infancy or early childhood, showing spontaneous remission in a subset of patients, while others develop lifelong disease. Despite an increased understanding of AD, factors guiding its natural course are only insufficiently elucidated. We thus performed suction blistering in skin of adult patients with stable, spontaneous remission from previous moderate-to-severe AD during childhood. Samples were compared to healthy controls without personal or familial history of atopy, and to chronic, active AD lesions. Skin cells and tissue fluid obtained were used for single-cell RNA sequencing and proteomic multiplex assays, respectively. We found overall cell composition and proteomic profiles of spontaneously healed AD to be comparable to healthy control skin, without upregulation of typical AD activity markers (e.g., IL13, S100As, and KRT16). Among all cell types in spontaneously healed AD, melanocytes harbored the largest numbers of differentially expressed genes in comparison to healthy controls, with upregulation of potentially anti-inflammatory markers such as PLA2G7. Conventional T-cells also showed increases in regulatory markers, and a general skewing toward a more Th1-like phenotype. By contrast, gene expression of regulatory T-cells and keratinocytes was essentially indistinguishable from healthy skin. Melanocytes and conventional T-cells might thus contribute a specific regulatory milieu in spontaneously healed AD skin.
2021-02-15 | GSE162054 | GEO
Project description:Atopic dermatitis (AD) typically starts in infancy or early childhood, showing spontaneous remission in a subset of patients, while others develop lifelong disease. Despite an increased understanding of AD, factors guiding its natural course are only insufficiently elucidated. We thus performed suction blistering in skin of adult patients with stable, spontaneous remission from previous moderate-to-severe AD during childhood. Samples were compared to healthy controls without personal or familial history of atopy, and to chronic, active AD lesions. Skin cells and tissue fluid obtained were used for single-cell RNA sequencing and proteomic multiplex assays, respectively. We found overall cell composition and proteomic profiles of spontaneously healed AD to be comparable to healthy control skin, without upregulation of typical AD activity markers (e.g., IL13, S100As, and KRT16). Among all cell types in spontaneously healed AD, melanocytes harbored the largest numbers of differentially expressed genes in comparison to healthy controls, with upregulation of potentially anti-inflammatory markers such as PLA2G7. Conventional T-cells also showed increases in regulatory markers, and a general skewing toward a more Th1-like phenotype. By contrast, gene expression of regulatory T-cells and keratinocytes was essentially indistinguishable from healthy skin. Melanocytes and conventional T-cells might thus contribute a specific regulatory milieu in spontaneously healed AD skin.
| S-EPMC7943477 | biostudies-literature
Project description:mRNA array analysis of total RNA from primary kertinocytes from three healthy controls, three atopic dermatitis patients and three psoriasis patients was carried out
2012-06-01 | E-MTAB-728 | biostudies-arrayexpress
Project description:mRNA array analysis was carried out using total RNA of skin biopsies from lesional and non-lesional skin of three atopic dermatitits patients and four healthy individuals.
2012-06-01 | E-MTAB-729 | biostudies-arrayexpress
Project description:Atopic dermatitis (AD) is a heritable inflammatory disease, characterised by skin barrier dysfunction. Genome-wide association studies (GWAS) have identified molecular targets with relevance for drug development, but the strongest genetic association, FLG, has not yet been successfully targeted in atopic disease. An AD-associated locus on chromosome 11q13.5 lies between two genes - EMSY and LRRC32 - but the functional mechanisms leading to AD are unclear. We applied a combination of genomic and molecular analytical techniques followed up in patient biopsies, to investigate pathomechanisms at this GWAS locus. Chromosome conformation capture data in keratinocytes shows interaction of the intergenic region in threedimensional space with EMSY. siRNA-mediated knockdown of EMSY in skin organoid culture leads to enhanced development of barrier function, measured by water evaporation and dye penetration. Global proteomic analysis of skin organoids with EMSY knockdown shows increased expression of structural and functional proteins, confirmed by histological and ultrastructural features. Lipid analysis shows an increase in ceramides known to be reduced in AD. Conversely, over-expression of EMSY in primary human keratinocytes leads to a reduction in biomarkers of barrier formation. Finally, skin biopsy samples from patients with AD show greater EMSY staining in the nucleus, consistent with increased functional effect of this DNAbinding protein. Together our findings demonstrate an important role for EMSY in transcriptional regulation and skin barrier formation, supporting EMSY inhibition as a therapeutic approach for AD.
2019-06-24 | PXD014088 | Pride
Project description:To generate novel atopic dermatitis model, we used Nestin-cre mediated Ikk2FL/FL mice. Nestincre-mediated conditional knockout mice of Ikk2 gene were generated by crossing female Ikk2FL/FL mice to male Nestin-cre;Ikk2FL/+mice. Nestin-cre;Ikk2FL/FL mice spontaneously develop chronic AD-like skin inflammation and severe pruritus. We further performed Cap analysis of gene expression (CAGE) to elucidate transcriptional profiles in lesional skin of Nestin-cre;Ikk2FL/FL mice.
2020-01-26 | GSE109936 | GEO
Project description:Atopic Dermatitis Research Network
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Project description:TWEAK Upregulates atopic dermatitis related genes in human kearatinocytes
2023-11-28 | GSE214503 | GEO
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:Clinical overlaps between psoriasis and atopic dermatitis are sometimes undiscernible, and there is no consensus whether to treat the overlap phenotype as psoriasis or atopic dermatitis. We enrolled patients diagnosed with either psoriasis or atopic dermatitis, and clinically re-stratified them into classic psoriasis, classic atopic dermatitis, and the overlap phenotype between psoriasis and atopic dermatitis. We compared gene expression profiles of lesional and nonlesional skin biopsy tissues between the three comparison groups. Global mRNA expression and T-cell subset cytokine expression in the skin of the overlap phenotype were consistent with the profiles of psoriasis and different from the profiles of atopic dermatitis. Unsupervised k-means clustering indicated that the best number of distinct clusters for the total population of the three comparison groups was two, and the two clusters of psoriasis and atopic dermatitis were differentiated by gene expression. Our study suggests that clinical overlap phenotype between psoriasis and atopic dermatitis has dominant molecular features of psoriasis, and genomic biomarkers can differentiate psoriasis and atopic dermatitis at molecular levels in patients with a spectrum of psoriasis and atopic dermatitis.
2023-06-24 | GSE182740 | GEO