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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 2

Murine AA compared with UA skin displays distinct composition and gene expression of APCs.

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Murine AA compared with UA skin displays distinct composition and gene e...
(A) UMAP plot of the flow-sorted CD45+ murine immune cells focusing on APC clusters: cluster 8 (n = 605) and cluster 13 (n = 109). (B) Unsupervised PCA of ssGSEA APC and Langerhans cell signatures and pathways. (C) ssGSEA enrichment scores for selected signaling pathways comparing UA with AA samples. (D) mRNA expression superimposed on the UMAP plot with canonical markers for APC lineages. (E) UMAP plot for APC cells after scaling mRNA for cell cycle difference. Cluster ID based on gene expression of markers. (F) UMAP plots for AA and UA cells across the new APC clusters with relative contribution of each cluster by UA versus AA sample and skin versus lymph node cells across all single cells, χ2 test; P value less than 0.05 for both comparisons.

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