Single-Cell Analysis of Temporal Immune Cell Dynamics in Alopecia Areata Reveals a Causal Role for Clonally Expanded CD8+ T Cells in Disease

    June 2025 in “ Cell Reports
    Zhenpeng Dai, Yuqian Chang, Eunice Lee, Valia P Leifer, Eddy Hsi Chun Wang, Rolando Pérez‐Lorenzo, Annemieke de Jong, Angela M. Christiano
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    Studysummary In this study using the C3H/HeJ mouse model of alopecia areata, researchers found that hyperexpanded CD8<sup>+</sup> T cell clones were sufficient to initiate disease, establishing a causal link between T cell clonality and pathogenicity.
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    This study explores the role of clonally expanded CD8+ T cells in alopecia areata (AA) using a mouse model, revealing that these cells are crucial for disease onset and progression. Through single-cell RNA and TCR sequencing, the research shows that hyperexpanded CD8+ T cell clones express high levels of cytotoxic molecules, correlating with disease severity. The introduction of TCR sequences from these clones into mice induced AA, establishing a causal link. Antibody-mediated depletion of these clones prevented and slowed AA progression, suggesting potential therapeutic strategies targeting these T cells. Despite limitations, the study underscores the importance of addressing persistent T cell clones to prevent disease recurrence.
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