Cellular and Molecular Changes in Psoriasis Lesions Induced by Ustekinumab: Distinct Differences in Responders vs. Non-Responders
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PROVIDER: PRJNA418753 | ENA |
REPOSITORIES: ENA
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Project description:A gene expression profiling sub-study was conducted in which skin biopsy samples (n=192) were collected for RNA extraction and hybridization to microarrays from patients with moderate-to-severe psoriasis who participated in ACCEPT, an IRB-approved Phase 3, multicenter, randomized trial. This analysis identified gene expressions significantly modulated in psoriasis lesions (LS) following ustekinumab or etanercept treatment at week 12 compared to baseline. Molecular expression of mRNA was found to be different in ustekinumab PASI75 responders vs. nonresponders. Differential modulation of selected mRNAs was also observed between ustekinumab and etanercept PASI75 responders.
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Project description:Ustekinumab provides clinical benefit to psoriasis patients, but precise cellular and molecular changes underlying its therapeutic utility are not yet fully understood. To assess differences between ustekinumab responders vs. non responders in modulating specific inflammatory pathways and provide reference data for exploring molecular effects of next-generation interleukin(IL)-17 and IL-23-antagonists in psoriasis.
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Project description:Cellular and Molecular Changes in Psoriasis Lesions Inducedby Ustekinumab: Distinct Differences in Responders vs. Non responders
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Project description:Coronavirus disease 2019 (COVID-19) primarily affects the respiratory system but extrapulmonary manifestations, including the skin, have been well documented. However, transcriptomic profiles of skin lesions have not been performed thus far. Here, we present a single-cell RNA sequencing analysis in a patient with COVID-19 infection with a maculopapular skin rash while on treatment with the interleukin (IL)-12/IL-23 blocker ustekinumab for underlying psoriasis. Results were compared with healthy controls and untreated psoriasis. We found the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral entry receptors ACE2 and TMPRSS2 in keratinocytes of the patient with COVID-19, while ACE2 expression was low to undetectable in psoriasis lesions and healthy skin. Among all cell types, ACE2+ keratinocyte clusters showed the highest levels of transcriptomic dysregulation in COVID-19, expressing type 1–associated immune markers such as CXCL9 and CXCL10. In line with a generally type 1–skewed immune microenvironment, cytotoxic lymphocytes showed increased expression of the IFNG gene and other T-cell effector genes, while type 2, type 17, or type 22 T-cell activation was largely absent. Conversely, downregulation of several anti-inflammatory mediators was observed. This first transcriptomic description of a COVID-19-associated rash identifies ACE2+ keratinocytes displaying profound transcriptional changes, and inflammatory immune cells that might help to improve the understanding of SARS-CoV-2-associated skin conditions.
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Project description:Psoriasis is a chronic inflammatory skin disease characterized by marked proliferation of keratinocytes leading to pronounced epidermal hyperplasia, elongation of rete ridges and hyperkeratosis. The most common form of psoriasis, chronic plaque psoriasis (Psoriasis vulgaris), involves relatively stable occurrence and progression of sharply demarcated lesions, usually on the trunk and extremities, which share a combination of trademark histological features, including tortuous and dilated dermal capillaries, loss of the epidermal granular layer, and accumulation of neutrophils beneath parakeratotic scale. In this study, whole-genome transcriptional profiling was used to characterize gene expression in 4 lesional and uninvolved skin samples obtained from patients with stable chronic plaque psoriasis. Skin mRNA expression was analysed by microarray. Four individuals with chronic plaque psoriasis were enrolled. 6 mm punch biopsies were obtained under local anaesthesia (lidocaine) from uninvolved skin and a target plaque.
2013-12-10 | E-GEOD-50790 | biostudies-arrayexpress
Project description:Psoriasis is characterized by hyperplasia and disrupted differentiation of keratinocytes. Keratinocytes are considered not only the target but also the critical participants. To explore the role of keratinocytes in psoriasis, we used microarrays to compared gene expression profile of epidermis between psoriasis lesions and healthy normal skin.
2021-02-09 | GSE166388 | GEO
Project description:Psoriasis is a chronic inflammatory skin disease characterized by marked proliferation of keratinocytes leading to pronounced epidermal hyperplasia, elongation of rete ridges and hyperkeratosis. The most common form of psoriasis, chronic plaque psoriasis (Psoriasis vulgaris), involves relatively stable occurrence and progression of sharply demarcated lesions, usually on the trunk and extremities, which share a combination of trademark histological features, including tortuous and dilated dermal capillaries, loss of the epidermal granular layer, and accumulation of neutrophils beneath parakeratotic scale. In this study, whole-genome transcriptional profiling was used to characterize gene expression in 4 lesional and uninvolved skin samples obtained from patients with stable chronic plaque psoriasis.Skin mRNA expression was analysed by microarray.
2013-12-10 | GSE50790 | GEO
Project description:Oral Banzhilian Formula (BZLF) is effective in the clinical treatment of psoriasis. However, the effectiveness and mechanism of different drug delivery routes deserve further study. In this study, we externally applied BZLF to the skin lesions in an IMQ-induced psoriasis mice model, and found that BZLF alleviated the psoriasis-like skin lesions, while inhibiting the expression of Ki67 and inflammatory factors (Il17a, Tnf-α, S100a7 and Cxcl1) in the skin lesions. Finally, through transcriptome sequencing combined with bioinformatics and other methods, it was found that the mechanism of action of BZLF against psoriasis is achieved by down-regulating the LCN2/MMP-9 axis. Overall, this study elucidates the effectiveness and mechanism of external application of BZLF in the treatment of psoriasis, and provided a new approach and basis for clinical application.
2023-03-29 | GSE223468 | GEO
Project description:Scalp psoriasis shows a variable clinical spectrum and in many cases poses a great therapeutic challenge. However, it remains unknown whether the immune response of scalp psoriasis differs from understood pathomechanisms of psoriasis on other skin areas. We sought to determine the cellular and mollecular phenotype of scalp psoriasis by performing a comparative analysis of scalp vs skin using lesional and nonlesional samples from 20 Caucasian subjects with untreated moderate to severe psoriasis and significant scalp involvement, and 10 control subjects without psoriasis. Our results suggest that even in the scalp psoriasis is a disease of the inter-follicular skin. The immune mechanisms that mediate scalp psoriasis were found to be similar to those involved in skin psoriasis. However, the magnitude of dysregulation, number of differentially expressed genes, and enrichment of the psoriatic genomic fingerprinting were more prominent in skin lesions. Furthermore, the scalp transcriptome showed increased modulation of several gene-sets, particularly those induced by interferon-gamma, compared with skin psoriasis which was mainly associated with activation of TNFâµ/L-17/IL-22-induced keratinocyte response genes. We also detected differences in expression of gene-sets involving negative regulation, epigenetic regulation, epidermal differentiation, and dendritic cell or Th1/Th17/Th22-related T-cell processes. To define the transcriptomic profile of scalp skin, punch biopsies (6 mm diameter) were obtained from 20 Caucasian patients with untreated moderate to severe psoriasis with significative scalp involvement and 10 control subjects without psoriasis (N). Lesional (LS) samples were isolated from the infiltrated border of a plaque of psoriasis. Non lesional (NL) samples were taken from scalp areas with no visible psoriasis between the infiltrated plaques.
2015-11-25 | E-GEOD-75343 | biostudies-arrayexpress
Project description:Scalp psoriasis shows a variable clinical spectrum and in many cases poses a great therapeutic challenge. However, it remains unknown whether the immune response of scalp psoriasis differs from understood pathomechanisms of psoriasis on other skin areas. We sought to determine the cellular and mollecular phenotype of scalp psoriasis by performing a comparative analysis of scalp vs skin using lesional and nonlesional samples from 20 Caucasian subjects with untreated moderate to severe psoriasis and significant scalp involvement, and 10 control subjects without psoriasis. Our results suggest that even in the scalp psoriasis is a disease of the inter-follicular skin. The immune mechanisms that mediate scalp psoriasis were found to be similar to those involved in skin psoriasis. However, the magnitude of dysregulation, number of differentially expressed genes, and enrichment of the psoriatic genomic fingerprinting were more prominent in skin lesions. Furthermore, the scalp transcriptome showed increased modulation of several gene-sets, particularly those induced by interferon-gamma, compared with skin psoriasis which was mainly associated with activation of TNF↵/L-17/IL-22-induced keratinocyte response genes. We also detected differences in expression of gene-sets involving negative regulation, epigenetic regulation, epidermal differentiation, and dendritic cell or Th1/Th17/Th22-related T-cell processes.
2015-11-25 | GSE75343 | GEO