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A transcriptomic map of murine and human alopecia areata
Nicholas Borcherding, Sydney B. Crotts, Luana S. Ortolan, Nicholas Henderson, Nicholas L. Bormann, Ali Jabbari
Nicholas Borcherding, Sydney B. Crotts, Luana S. Ortolan, Nicholas Henderson, Nicholas L. Bormann, Ali Jabbari
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Research Article Immunology

A transcriptomic map of murine and human alopecia areata

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Abstract

Alopecia areata (AA) is a common autoimmune condition, presenting initially with loss of hair without other 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 murine AA. We found clonal expansions of both CD4+ and CD8+ T cells, with shared clonotypes across varied transcriptional states. The murine AA 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.

Authors

Nicholas Borcherding, Sydney B. Crotts, Luana S. Ortolan, Nicholas Henderson, Nicholas L. Bormann, Ali Jabbari

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Figure 6

Human single-cell immune profiling of AA T cells recapitulates the findings of the murine analysis.

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Human single-cell immune profiling of AA T cells recapitulates the findi...
(A) UMAP plot of the T cell isolated from human AA skin (n = 1664) and control skin (n = 752). (B) Relative contribution of cells to each cluster from normal versus AA samples for all single cells. (C) Normalized correlation values for predicted immune cell phenotypes based on the SingleR R package for each cluster. (D) mRNA expression superimposed on the UMAP plots for lineage and functional markers for T cell populations. (E) Expression comparison and distribution of selected signature markers superimposed on the UMAP plot. (F) Z score–transformed ssGSEA enrichment scores for selected pathways by T cell cluster. (G) The percentage of the top 100 clonotypes that is occupied by the top 1–10, 11–20, 21–40, and 41–100 clones for human AA and control skin. (H) ssGSEA enrichment skin-derived T lymphocytes by grouping the number of repeated clonotypes: 1 (unique clonotypes, AA n = 907, control n = 389), 2–15 (AA n = 262, control n = 122), and 16 or greater (AA n = 51, control n = 0); 1-way ANOVA used for comparison across all clonotype groups.

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