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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 3

Identification of murine T cell populations in skin and lymph nodes.

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Identification of murine T cell populations in skin and lymph nodes.
(A)...
(A) Total cell UMAP plot and UMAP separated by tissue and condition for flow-sorted CD45+ murine immune cells focusing on T cell cluster: cluster 1 (n = 1301), cluster 2 (n = 1159), cluster 3 (n = 960), cluster 4 (n = 897), cluster 6 (n = 869), and cluster 7 (n = 681). (B) Relative contribution of cells to each cluster from lymph node versus skin (upper panel) and from UA versus AA samples for all single cells. (C) mRNA expression superimposed on the UMAP plot for general T cell markers (upper and middle rows) and Tregs (bottom row). (D) UMAP plot of the T cell phenotype labels based on gene expression and pathway analysis. (E) Genes from the predictive ALADIN (4) for CTL and IFN. Genes not expressed in T cells are in gray. (F) ssGSEA enrichment scores for selected pathways by T cell cluster; 1-way ANOVA used for comparison across all clusters.

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