Transcriptomic Analysis of Human Epidermal Keratinocytes Stimulated with TWEAK, TNF and IL-17A
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE171170 | GEO | 2021/11/19
REPOSITORIES: GEO
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Project description:Transcriptomic Analysis of Human Epidermal Keratinocytes Stimulated with TWEAK, TNF and IL-17A
| PRJNA718582 | ENA
Project description:Atopic dermatitis and psoriasis are driven by alternate type 2 and type 17 immune responses, but some proteins might be critical to both diseases. We show that a deficiency of the TNF superfamily molecule TWEAK (TNFSF12) in mice results in defective maintenance of atopic dermatitis-specific Th2 and psoriasis-specific Th17 cells in the skin, and impaired expression of disease-characteristic chemokines and cytokines, such as CCL17 and TSLP in atopic dermatitis, and CCL20 and IL-19 in psoriasis. The TWEAK receptor, Fn14, is upregulated in keratinocytes and dermal fibroblasts, and TWEAK induces these cytokines and chemokines alone and in synergy with the signature T helper cytokines of either disease, IL-13 and IL-17. Furthermore, subcutaneous injection of recombinant TWEAK into naïve mice induces cutaneous inflammation with histological and molecular signs of both diseases. TWEAK is therefore a critical contributor to skin inflammation and a possible therapeutic target in atopic dermatitis and psoriasis.
2017-05-01 | GSE96957 | GEO
Project description:The clinical features of psoriasis, characterized by sharply demarcated scaly erythematous plaques, are typically so distinctive that a diagnosis can easily be made on these grounds alone. However, there is great variability in treatment response between individual patients, and this may reflect heterogeneity of inflammatory networks driving the disease. In this study, whole-genome transcriptional profiling was used to characterize inflammatory and cytokine networks in 62 lesional skin samples obtained from patients with stable chronic plaque psoriasis. We were able to stratify lesions according to their inflammatory gene expression signatures, identifying those associated with strong (37% of patients), moderate (39%) and weak inflammatory infiltrates (24%). Additionally, we identified differences in cytokine signatures with heightened cytokine-response patterns in one sub-group of lesions (IL-13-strong; 50%) and attenuation of these patterns in a second sub-group (IL-13-weak; 50%). These sub-groups correlated with the composition of the inflammatory infiltrate, but were only weakly associated with increased risk allele frequency at some psoriasis susceptibility loci (e.g., REL, TRAF3IP2 and NOS2). Our findings highlight variable points in the inflammatory and cytokine networks known to drive chronic plaque psoriasis. Such heterogeneous aspects may shape clinical course and treatment responses, and can provide avenues for development of personalized treatments. We used Affymetrix microarrays to evaluate genome-wide expression in primary human keratinocytes exposed to cytokines. Cytokine activity signatures were used to interpret the shifts in gene expression that occur in psoriasis plaques relative to normal uninvolved skin. Primary keratinocytes from three donors (subjects 1, 2, and 3) were obtained and were either untreated (control) or exposed to cytokines (IL-4, IL-13, IFN-alpha, IFN-gamma and TNF). For the IL17A samples, primary keratinocytes were obtained from six donors, with cells derived from three donors treated with IL-17A and cells derived from the other three donors left untreated (i.e., unpaired control samples).
2012-03-07 | E-GEOD-36287 | biostudies-arrayexpress
Project description:IL-17C is important for the pathogenesis of inflammatory diseases such as IBD and psoriasis. We found that IL-17C is highly induced in a murine model of psoriasis. Recent results suggest that IL-17C can target epithelial cells that express both IL-17RA and IL-17RE receptor chains. Here we identify genes induced in response to IL-17C treatment of human keratinocytes to provide the tools for dissection of the IL-17C signaling pathway. Human keratinocytes, HEKn, were incubated in the absence (n = 3) and presence (n = 5) of 500 ng/ml recombinant human IL-17C for 3 and 24 hours. Whole RNA was isolated via RNeasy kit (Qiagen).
2011-10-11 | E-GEOD-32620 | biostudies-arrayexpress
Project description:This study aims to define the interactions that SA or SP may have with IL-17A and TNF-α in human keratinocytes, as well as the similarity to psoriasis vulgaris
2023-03-24 | GSE207390 | GEO
Project description:IL-17C is important for the pathogenesis of inflammatory diseases such as IBD and psoriasis. We found that IL-17C is highly induced in a murine model of psoriasis. Recent results suggest that IL-17C can target epithelial cells that express both IL-17RA and IL-17RE receptor chains. Here we identify genes induced in response to IL-17C treatment of human keratinocytes to provide the tools for dissection of the IL-17C signaling pathway.
2011-10-12 | GSE32620 | GEO
Project description:In this study we tested interactions between IL-36 and IL-17A in human keratinocytes. 24 hours of IL-36 stimulation in keratinocytes promoted IL-36, IL-17C, and characteristic psoriasis-related molecule expressions in normal human epidermal keratinocytes in dose-dependent manners as measured by mRNA and protein quantification.
2021-12-31 | GSE160904 | GEO
Project description:The clinical features of psoriasis, characterized by sharply demarcated scaly erythematous plaques, are typically so distinctive that a diagnosis can easily be made on these grounds alone. However, there is great variability in treatment response between individual patients, and this may reflect heterogeneity of inflammatory networks driving the disease. In this study, whole-genome transcriptional profiling was used to characterize inflammatory and cytokine networks in 62 lesional skin samples obtained from patients with stable chronic plaque psoriasis. We were able to stratify lesions according to their inflammatory gene expression signatures, identifying those associated with strong (37% of patients), moderate (39%) and weak inflammatory infiltrates (24%). Additionally, we identified differences in cytokine signatures with heightened cytokine-response patterns in one sub-group of lesions (IL-13-strong; 50%) and attenuation of these patterns in a second sub-group (IL-13-weak; 50%). These sub-groups correlated with the composition of the inflammatory infiltrate, but were only weakly associated with increased risk allele frequency at some psoriasis susceptibility loci (e.g., REL, TRAF3IP2 and NOS2). Our findings highlight variable points in the inflammatory and cytokine networks known to drive chronic plaque psoriasis. Such heterogeneous aspects may shape clinical course and treatment responses, and can provide avenues for development of personalized treatments. We used Affymetrix microarrays to evaluate genome-wide expression in primary human keratinocytes exposed to cytokines. Cytokine activity signatures were used to interpret the shifts in gene expression that occur in psoriasis plaques relative to normal uninvolved skin.
2012-03-07 | GSE36287 | GEO
Project description:In psoriasis lesions, a diverse mixture of cytokines is upregulated which influence each other generating a complex inflammatory situation. Although this is the case, the inhibition of Interleukin-17A (IL-17A) alone showed unprecedented clinical results in patients, indicating that IL-17A is a critical inducer of psoriasis pathogenesis. To elucidate IL-17A-driven keratinocyte-intrinsic signaling pathways, we treated monolayers of normal human epidermal keratinocytes in vitro with a mixture of 6 cytokines (IL-17A, TNF-a, IL-17C, IL-22, IL-36g and IFN-g) involved in psoriasis, to mimic the inflammatory milieu in psoriasis lesions. Microarray and gene set enrichment analysis revealed that this cytokine mixture induced similar gene expression changes with the previous transcriptome studies using psoriasis lesions. Importantly, we identified a set of IL-17A-regulated genes in keratinocytes, which recapitulate typical psoriasis genes exemplified by DEFB4A, S100A7, IL19 and CSF3, based on differences in the expression profiles of cells stimulated with 6 cytokines versus cells stimulated with only 5 cytokines lacking IL-17A. Furthermore a specific IL-17A-induced gene, NFKBIZ, which encodes IkappaB-zeta, a transcriptional regulator for NF-kappaB, was demonstrated to have a significant role for IL-17A-induced gene expression. Thus, we present novel in vitro data from normal human keratinocytes that would help elucidating the IL-17A-driven keratinocyte activation in psoriasis. Cytokine mixture-induced gene expression in primary normal human epidermal keratinocytes (NHEKs) was measured at 24 hours after exposure. NHEKs were exposed to the combination of selected six cytokines (IL-17A: 100 ng/ml, TNF-a: 10 ng/ml, IFN-g: 10 ng/ml, IL-17C: 100 ng/ml, IL-22: 100 ng/ml, IL-36g: 500 ng/ml) , or to the different combinations of five of the six cytokines (in total, 7 different treatments and one untreated control). No replicate experiments were conducted.
2016-03-08 | E-GEOD-77719 | biostudies-arrayexpress
Project description:In 2019, our group performed small RNA-sequencing on keratinocytes isolated from lesional and non-lesional psoriasis skin as well as from healthy skin, and identified miRNAs with altered levels in psoriasis keratinocytes (Srivastava et al., 2019). One of the miRNAs we identified to be overexpressed in psoriasis keratinocytes was miR-378a-3p. In this study, we aimed to explore the regulation and function of miR-378a in keratinocytes and its potential role in psoriasis. We used microarrays to identify differentially expressed genes upon miR-378a overexpression in primary human keratinocytes as part of the study and gain insights about the modulation of specific pathways.
2021-03-08 | GSE164400 | GEO