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MiRNA profiling of C3H/HeJ mice with and without spontaneous alopecia areata

ABSTRACT: Our goal was to identify miRNA expression patterns that correlated with spontaneous onset of autoimmune alopecia in C3H/HeJ mice compare to normal haired controls. Skin from 3 mice with or without spontaneous AA were taken for the study.

ORGANISM(S): Mus musculus

PROVIDER: GSE94407 | GEO | 2017/02/03

SECONDARY ACCESSION(S): PRJNA369613

REPOSITORIES: GEO

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Effect of systemic exposure of JAK1 Inhibition (AZ13748709) in C3H/HeJ Mice with Alopecia Areata In Vivo

Project description:JAK inhibition by means of clinically available pan JAK inhibitors has recently demonstrated great efficacy in both restoring hair growth and resolving inflammation in the skin of patients with Alopecia Areata (AA). These effects are dose dependent and mainly efficacious at ranges close to a questionable risk profile. Given the great responses to JAK inhibition and the current lack of efficacious treatments in AA, it is exciting to explore the possibilities to separate the beneficial and adverse effects in order to provide a successful treatment option for these patients where the medical need is still vastly unmet. We have demonstrated that specific inhibition of JAK1 at relevant concentrations produces a fast resolution of inflammation and complete restoration of hair growth in the C3H/HeJ model of AA and importantly, that systemic exposure is essential for efficacy.

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Project description: Not available

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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

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