A transcriptomic map of murine and human alopecia areata.

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

doi:10.1172/jci.insight.137424

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.

Highlights

Alopecia areata (AA) is a common autoimmune condition, affecting an estimated 6 million people in the United States [1], and has a total lifetime risk of approximately 2% [2]
The multiple sequencing runs were combined into a single uniform manifold approximation and projection (UMAP) and identified 15 immune cell clusters (Figure 1A)
Using the median gene expression for each cluster, each cluster was assigned to a cell lineage using 2 methods: (a) the correlation of murine pure-cell gene signatures derived from the Immunological Genome Project [20] (Figure 1D) and (b) the analysis of expression patterns of canonical markers (Figure 1E) for T cells (Cd3d, Cd28, Cd4, Cd8), antigen-presenting cells (APCs) (Itgax [CD11c], Itgam [CD11b], Xcr1, Cd207 [Langerin]), and B cells (Cd79a, Cd19)

Summary

Introduction

Alopecia areata (AA) is a common autoimmune condition, affecting an estimated 6 million people in the United States [1], and has a total lifetime risk of approximately 2% [2]. Broad-acting immunosuppressants have been used with unreliable outcomes and minimal efficacy, especially in those with severe presentations. Recent genomic investigations [4] and gene expression profiling studies [5] have led to clinical trials involving JAK molecule– targeted therapies [6,7,8]. These emerging clinical trials have shown efficacy in the treatment of AA, an increasing spectrum of worrisome side effects associated with these inhibitors is being recognized [9]. Despite the overall prevalence and well-defined clinical presentation, the underlying pathogenesis of AA is not fully understood and has limited further innovation for AA therapeutics

Methods

Results

Conclusion