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Functional interrogation of lymphocyte subsets in alopecia areata using single-cell RNA sequencing

ABSTRACT: Functional interrogation of lymphocyte subsets in alopecia areata using single-cell RNA sequencing

PROVIDER: PRJNA978553 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24795319_1.fastq.gz	Fastqsanger.gz
	SRR24795319_2.fastq.gz	Fastqsanger.gz
	SRR24795320_1.fastq.gz	Fastqsanger.gz
	SRR24795320_2.fastq.gz	Fastqsanger.gz
	SRR24795321_1.fastq.gz	Fastqsanger.gz

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Functional interrogation of lymphocyte subsets in alopecia areata using single-cell RNA sequencing

Project description:Alopecia areata (AA) is among the most prevalent autoimmune diseases, but the development of innovative therapeutic strategies has lagged due to an incomplete understanding of the immunological underpinnings of disease. Here, we performed single-cell RNA sequencing (scRNAseq) of skin-infiltrating immune cells from the graft-induced C3H/HeJ mouse model of AA, coupled with antibody-based depletion to interrogate the functional role of specific cell types in AA in vivo. Since AA is predominantly T cell-mediated, we focused on dissecting lymphocyte function in AA. Both our scRNAseq and functional studies established CD8+ T cells as the primary disease-driving cell type in AA. Only the depletion of CD8+ T cells, but not CD4+ T cells, NK, B, or γδ T cells, was sufficient to prevent and reverse AA. Selective depletion of regulatory T cells (Treg) showed that Treg are protective against AA in C3H/HeJ mice, suggesting that AA failure of Treg-mediated immunosuppression is not a major disease mechanism. Focused analyses of CD8+ T cells revealed five subsets, whose heterogeneity is defined by an ‘effectorness gradient’ of interrelated transcriptional states that culminate in increased effector function and tissue residency. scRNAseq of human AA skin showed that CD8+ T cells in human AA follow a similar trajectory, underscoring that shared mechanisms drive disease in both murine and human AA. Our study represents a comprehensive, systematic interrogation of lymphocyte heterogeneity in AA, and uncovers a framework for AA-associated CD8+ T cells with implications for the design of future therapeutics.

2023-07-25 | GSE233906 | GEO

First ruxolitinib treatment of human alopecia areata patients

Project description:Two patients with alopecia areata were treated with systemic ruxolitinib. Skin biopsies were taken before starting treatment and 12 weeks after starting treatment. We used microarrays to assess changes in gene expression of affected skin before and after starting treatment Two patients with alopecia areata were recruited for our study. Skin biopsies of affected scalp were taken prior to starting treatment with oral ruxolinitib. Additional skin biopsies were taken 12 weeks after starting treatment. Scalp skin biopsies were taken from patients without alopecia areata for comparison. RNA was extracted, cDNA libraries were made and profiled on affymetrix microarray chips.

2014-08-17 | E-GEOD-58573 | biostudies-arrayexpress

Human Alopecia Areata Skin Profiling

Project description:Our goal was to develop a transcriptomic description of affected alopecic scalp skin from patients with alopecia areata. 5 biological replicates of skin samples from 5 separate AA patients compared with 5 similar scalp samples from healthy control patients

2014-08-17 | E-GEOD-45512 | biostudies-arrayexpress

Human Alopecia Areata Skin Profiling

Project description:Our goal was to develop a transcriptomic description of affected alopecic scalp skin from patients with alopecia areata.

2014-08-17 | GSE45512 | GEO

Human Alopecia Areata Skin Biopsy Samples

Project description:Gene expression profiling of scalp skin biopsies from patients with alopecia areata or normal healthy controls Scalp skin punch biopsies were taken from the indicated patients and stored in PAXgene tissue containers for shipping to a central location, where the samples were processed

2017-02-09 | GSE68801 | GEO

Functional interrogation of lymphocyte subsets in alopecia areata using single-cell RNA sequencing.

Project description: Not available

| S-EPMC10629527 | biostudies-literature

First ruxolitinib treatment of human alopecia areata patients

2014-08-17 | GSE58573 | GEO

Pilot open label clinical trial of oral ruxolitinib in patients with alopecia areata

Project description:This goal of these studies were to examine gene expression profiles of skin from patients with alopecia areata undergoing treatment with oral ruxoltinib. Microarray analysis was performed to assess changes in gene expression in affected scalp skin.

2017-08-23 | GSE80342 | GEO

Genome Wide Association Study of Alopecia Areata

Project description:Genome Wide Association Study of Alopecia Areata

| PRJNA187262 | ENA

Extensive alopecia areata is reversed by IL-23 cytokine antagonism

Project description:Alopecia areata (AA) is a prevalent disease associated with major emotional distress, and lacks effective, safe therapeutics for patients with extensive hair loss. This is the first report of hair regrowth with specific cytokine antagonism, in three patients with extensive hair loss ranging from 40% scalp involvement to alopecia universalis. Ustekinumab, an IL-12/23p40 antagonist that is highly effective in psoriasis, showed impressive ability to induce hair regrowth, coupled with suppression of inflammatory pathways and upregulation of hair keratins. Our report suggests that extensive AA is reversible using targeted treatments, opening the door for specific cytokine antagonism for this debilitating disease. We evaluated hair regrowth in three AA patients at 20 weeks after treatment with 3 subcutaneous doses of 90mg ustekinumab given at weeks 0, 4, and 16. Skin biopsies of lesional and non-lesional scalp (when available) were taken at baseline (week 0) and at week 20. We also obtained biopsies from three healthy individuals.

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