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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 4

Murine AA T lymphocytes show greater shared repertoire and sustained CD4 activation.

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Murine AA T lymphocytes show greater shared repertoire and sustained CD4...
(A) Shared and unique clonotypes of T cells by cluster for UA samples as a chord diagram (left) and relative proportion bar chart. In the chord diagram, the larger the connection between the cluster, the greater the number of shared clonotypes. Dominant percentage overlap for each cluster is annotated in the bar graph. (B) Shared and unique clonotypes of T cells by cluster for AA samples as a chord diagram (left) and relative proportion bar chart. (C) Alluvial diagrams for the shared clonotypes between skin and lymph node T lymphocytes in skin-predominant T cell clusters. Cluster 2 (overlap coefficient = 7.7%) and cluster 6 (overlap coefficient = 45.5%) in AA had a greater shared repertoire than the UA samples, with overlap coefficients of 0% and 0%, respectively. Clonotypes with 2 or more copies highlighted in white; overlapping clonotypes between skin and lymph nodes highlighted in red. (D) ssGSEA enrichment skin-derived T lymphocytes by grouping the number of repeated clonotypes: 1 (unique clonotypes, AA n = 1056, UA n = 1830), 2–15 (AA n = 385, UA n = 219), and 16 or greater (AA n = 573, UA n = 303); 1-way ANOVA used for comparison across clonotype groups.

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