Single-cell analysis of temporal immune cell dynamics in alopecia areata reveals a causal role for clonally expanded CD8+ T cells in disease
Summary: Alopecia areata (AA) is an immune-mediated hair loss disorder characterized by the infiltration of immune cells, including clonally expanded CD8+ T cells into lesional skin. To explore the link between CD8+ T cell clonality and disease pathogenicity, we conducted single-cell RNA and T cell...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-07-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725005698 |
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| Summary: | Summary: Alopecia areata (AA) is an immune-mediated hair loss disorder characterized by the infiltration of immune cells, including clonally expanded CD8+ T cells into lesional skin. To explore the link between CD8+ T cell clonality and disease pathogenicity, we conducted single-cell RNA and T cell receptor (TCR) sequencing in the C3H/HeJ mouse model of AA. We analyzed T cells derived from skin and skin-draining lymph nodes to capture both the end-organ and the site of antigen priming and found striking hyper-expansion of T cell clones associated with disease onset. Using the hyperexpanded CD8+ TCR sequences, we generated TCR retrogenic mice engineered to express a single clonotypic T cell population, applied CRISPR-Cas9 to engineer these TCR sequences within CD8+ T cells, and performed depletion experiments to demonstrate that expanded CD8+ T cell clones are sufficient to initiate disease, establishing a causal relationship between CD8+ T cell clonality and pathogenicity in disease. |
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| ISSN: | 2211-1247 |