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Single-cell profiling of prurigo nodularis demonstrates immune-stromal crosstalk driving profibrotic responses and reversal with nemolizumab

ABSTRACT: Single-cell profiling of prurigo nodularis demonstrates immune-stromal crosstalk driving profibrotic responses and reversal with nemolizumab

PROVIDER: PRJNA1142407 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30049700_1.fastq.gz	Fastqsanger.gz
	SRR30049700_2.fastq.gz	Fastqsanger.gz
	SRR30049701_1.fastq.gz	Fastqsanger.gz
	SRR30049701_2.fastq.gz	Fastqsanger.gz
	SRR30049702_1.fastq.gz	Fastqsanger.gz

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Prurigo Nodularis

Project description:Prurigo Nodularis

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Single-cell profiling of prurigo nodularis demonstrates immune-stromal crosstalk driving profibrotic responses and reversal with nemolizumab

Project description:Prurigo nodularis (PN) is a chronic neuroimmune skin disease characterized by bilaterally distributed pruritic hyperkeratotic nodules on extremities and trunk. Neuroimmune dysregulation and chronic scratching are believed to both induce and maintain the characteristic lesions. This study sought to provide a comprehensive view of the molecular pathogenesis of PN at the single-cell level to identify and outline key pathologic processes and the cell types involved. Features that distinguish PN skin from the skin of patients with atopic dermatitis were of particular interest. We further aimed to determine the impact of the IL31RA antagonist, nemolizumab, and its specificity at the single-cell level.

2024-07-31 | GSE273559 | GEO

Gene expression Prurigo Nodularis

Project description:Prurigo nodularis is a debilitating skin condition that is characterized by chronic itch and a prolonged scratching behavior. Little is known of the underlying molecular mechanisms that initiate and maintain the desease. Therefore, we analyzed gene expression in prurigo patients and matched healthy controls.

2022-10-31 | GSE210829 | GEO

DNA methylation in Prurigo Nodularis

Project description:Prurigo nodularis is a debilitating skin condition that is characterized by chronic itch and a prolonged scratching behavior. Little is known of the underlying molecular mechanisms that initiate and maintain the desease. Therefore, we analyzed DNA methylation in prurigo patients and matched healthy controls.

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Gene expression Prurigo Nodularis

Project description:Gene expression Prurigo Nodularis

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DNA methylation in Prurigo Nodularis

Project description:DNA methylation in Prurigo Nodularis

| PRJNA867711 | ENA

Single-cell profiling of prurigo nodularis demonstrates immune-stromal crosstalk driving profibrotic responses and reversal with nemolizumab.

Project description:BackgroundPrurigo nodularis (PN) is a chronic neuroimmune skin disease characterized by bilaterally distributed pruritic hyperkeratotic nodules on extremities and trunk. Neuroimmune dysregulation and chronic scratching are believed to both induce and maintain the characteristic lesions.ObjectivesThis study sought to provide a comprehensive view of the molecular pathogenesis of PN at the single-cell level to identify and outline key pathologic processes and the cell types involved. Features that distinguish PN skin from the skin of patients with atopic dermatitis were of particular interest. We further aimed to determine the impact of the IL31RA antagonist, nemolizumab, and its specificity at the single-cell level.MethodsSingle-cell RNA-sequencing of skin from 15 healthy donors and nonlesional and lesional skin from 6 patients each with PN and atopic dermatitis, combined with spatial-sequencing using the 10x Visium platform. Integration with bulk RNA-sequencing data from patients treated with nemolizumab.ResultsThis study demonstrates that PN is an inflammatory skin disease characterized by both keratinocyte proliferation and activation of profibrotic responses. This study also demonstrates that the COL11A1+ fibroblast subset is a major contributor to fibrosis and is predominantly found in the papillary dermis of PN skin. Activation of fibrotic responses is the main distinguishing feature between PN and atopic dermatitis skin. This study further shows the broad effect of nemolizumab on PN cell types, with a prominent effect driving COL11A1+ fibroblast and keratinocyte responses toward normal.ConclusionsThis study provides a high-resolution characterization of the cell types and cellular processes activated in PN skin, establishing PN as a chronic fibrotic inflammatory skin disease. It further demonstrates the broad effect of nemolizumab on pathological processes in PN skin.

| S-EPMC11231883 | biostudies-literature

Single-cell RNA sequencing reveals dysregulated fibroblast subclusters in prurigo nodularis

Project description:Prurigo nodularis (PN) is an intensely pruritic, inflammatory skin disease with a poorly understood pathogenesis. Thus, we performed single-cell transcriptomic profiling of 28,695 lesional and non-lesional PN cells. Lesional PN has increased dysregulated fibroblasts (FBs) and myofibroblasts. FBs in lesional PN were shifted towards a cancer-associated fibroblast (CAF)-like phenotype, with POSTN+WNT5A+ CAFs increased in PN, and similarly so in squamous cell carcinoma. A multi-center cohort study revealed an increased risk of SCC and CAF-associated malignancies (breast and colorectal) in PN patients. Systemic fibroproliferative diseases (renal sclerosis and idiopathic pulmonary fibrosis) were upregulated in PN patients. Ligand receptor analyses demonstrated a fibroblast neuronal axis with FB-derived WNT5A and periostin interactions with neuronal receptors MCAM and ITGAV. Compared to atopic dermatitis and psoriasis, mesenchymal dysregulation is unique to PN with an intermediate Th2/Th17 phenotype. These findings identify a pathogenic and targetable POSTN+WNT5A+ fibroblast subpopulation that may predispose CAF-associated malignancies in PN patients.

2024-01-22 | GSE233280 | GEO

Single-cell transcriptome analysis of CD3+ T lymphocytes from prurigo nodularis lesional skin reveals Th17 polarization

Project description:Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by symmetrically distributed, intensely pruritic nodules of unknown etiology and unmet therapeutic need. The lack of approved therapies and the limited efficacy of off-label treatments reflect the current poor understanding of its pathogenesis. We aimed to comprehensively characterize the phenotypic variation of CD3+ T cells and asses cell-specific gene expression in the lesional skin of patients with PN versus in patients with atopic dermatitis (AD) and in healthy controls (HC). To this end, single-cell RNA sequencing (scRNA-Seq) using 10x Genomics was carried out to compare CD3+ T cells transcriptomic heterogeneity between lesional samples of PN (n=6), AD (n=5) and HC (n=5).

2023-07-08 | GSE213849 | GEO

Single-cell RNA sequencing reveals dysregulated fibroblast subclusters in prurigo nodularis

Project description:Single-cell RNA sequencing reveals dysregulated fibroblast subclusters in prurigo nodularis

| PRJNA975621 | ENA