Spatial transcriptomics of autoimmune alopecia
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE227632 | GEO | 2023/09/25
REPOSITORIES: GEO
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Project description:Scarring alopecia consists of a collection of disorders characterized by destruction of hair follicles, replacement with fibrous scar tissue, and irreversible hair loss. Alopecia affects men and women worldwide and can be a significant source of psychological stress and depression for affected individuals. The purpose of this study was to explore metabolic profiles in scalp tissue samples from normal control subjects (n=6) and in matched samples obtained from affected (n=12) and unaffected (n=12) areas of the scalp in patients with lymphocytic Frontal Fibrosing Alopecia (FFA). Frontal fibrosing alopecia results from destruction of hair follicles by an inflammatory lymphocytic infiltrate that is localized around the upper portion of the hair follicle.
2014-07-24 | ST000093 | MetabolomicsWorkbench
Project description:Alopecia areata (AA) is one of the most common autoimmune conditions, presenting initially with loss of hair without overt skin changes. The unremarkable appearance of the skin surface contrasts with the complex immune activity occurring at the hair follicle. AA pathogenesis is due to the loss of immune privilege of the hair follicle leading to autoimmune attack. Although the literature has focused on CD8+ T cells, vital roles for CD4+ T cells and antigen-presenting cells have been suggested. Here, we use single-cell sequencing to reveal distinct expression profiles of immune cells in AA. We found clonal expansions of both CD4+ and CD8+ T cells, with shared clonotypes across varied transcriptional states. These data were used to generate highly predictive models of human AA disease. Finally, single-cell sequencing of T cells in human AA recapitulated the clonotypic findings and the gene expression of the predictive models.
2020-08-10 | GSE145095 | GEO
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.
2015-12-08 | E-GEOD-74761 | biostudies-arrayexpress
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.
2015-12-08 | GSE74761 | GEO
Project description:The hair follicle stem cell niche is an immune-privileged microenvironment, characterized by reduced antigen presentation, thus shielding against permanent immune-mediated tissue damage. In this study, we demonstrated the protective role of hair follicle-specific epidermal growth factor receptor (EGFR) against scarring hair follicle destruction. Mechanistically, disruption of EGFR signalling generated a cell-intrinsic hypersensitivity within the JAK-STAT1 pathway, which, synergistically with interferon gamma expressing CD8 T-cell and NK-cell-mediated inflammation, compromised the stem cell niche. Hair follicle-specific genetic depletion of either JAK1/2 or STAT1 or therapeutic inhibition of JAK1/2 ameliorated the inflammation, restored skin barrier function and activated the residual stem cells to resume hair growth in mouse models of epidermal and hair follicle-specific EGFR deletion. Skin biopsies from EGFR inhibitor-treated and cicatricial alopecia patients indicated active STAT1 signalling and interferon target expression. Notably, a case study of folliculitis decalvans, characterized by progressive hair loss, scaling and perifollicular erythema, demonstrated successful treatment with JAK1/2 inhibition. Our findings offer molecular insights and present a mechanism-based therapeutic strategy for addressing chronic folliculitis associated with EGFR-inhibitor anti-cancer therapy and cicatricial alopecia.
2024-07-31 | GSE273572 | GEO
Project description:The hair follicle stem cell niche is an immune-privileged microenvironment, characterized by reduced antigen presentation, thus shielding against permanent immune-mediated tissue damage. In this study, we demonstrated the protective role of hair follicle-specific epidermal growth factor receptor (EGFR) against scarring hair follicle destruction. Mechanistically, disruption of EGFR signalling generated a cell-intrinsic hypersensitivity within the JAK-STAT1 pathway, which, synergistically with interferon gamma expressing CD8 T-cell and NK-cell-mediated inflammation, compromised the stem cell niche. Hair follicle-specific genetic depletion of either JAK1/2 or STAT1 or therapeutic inhibition of JAK1/2 ameliorated the inflammation, restored skin barrier function and activated the residual stem cells to resume hair growth in mouse models of epidermal and hair follicle-specific EGFR deletion. Skin biopsies from EGFR inhibitor-treated and cicatricial alopecia patients indicated active STAT1 signalling and interferon target expression. Notably, a case study of folliculitis decalvans, characterized by progressive hair loss, scaling and perifollicular erythema, demonstrated successful treatment with JAK1/2 inhibition. Our findings offer molecular insights and present a mechanism-based therapeutic strategy for addressing chronic folliculitis associated with EGFR-inhibitor anti-cancer therapy and cicatricial alopecia.
2024-07-31 | GSE273571 | GEO
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
Project description:Spatial transcriptomics of autoimmune alopecia
| PRJNA945938 | ENA
Project description:Background: Alopecia areata (AA) is considered a highly heritable, T-cell-mediated autoimmune disease of the hair follicle. However, no convincing susceptibility gene has yet been pinpointed in the major histocompatibility complex (MHC), a genome region known to be associated with AA as compared to other regions. Methods: We engineered mice carrying AA risk allele identified by haplotype sequencing for the MHC region using allele-specific genome editing with the CRISPR/Cas9 system. Finally, we performed functional evaluations in the mice and AA patients with and without the risk allele. Findings: We identified a variant (rs142986308, p.Arg587Trp) in the coiled-coil alpha-helical rod protein 1 (CCHCR1) gene as the only non-synonymous variant in the AA risk haplotype. Furthermore, mice engineered to carry the risk allele displayed a hair loss phenotype. Transcriptomics further identified CCHCR1 as a novel component interacting with hair cortex keratin in hair shafts. Both, these alopecic mice and AA patients with the risk allele displayed morphologically impaired hair and comparable differential expression of hair-related genes, including hair keratin and keratin-associated proteins (KRTAPs). Interpretation: Our results implicate CCHCR1 with the risk allele in a previously unidentified subtype of AA based on aberrant keratinization in addition to autoimmune events.
2021-12-31 | GSE149653 | GEO
Project description:Microbiome in the hair follicle of androgenetic alopecia patients
| PRJEB22474 | ENA