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Single cell transcriptome profiling reveals pathogenesis of bullous pemphigoid.
Guirong Liang1, Chenjing Zhao1, Qin Wei1
1Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.
Communications Biology
|February 8, 2025
Summary
Bullous pemphigoid (BP) involves significant immune and non-immune cell changes in skin and blood. This study reveals key cellular pathways and immune cell shifts during BP progression and remission, offering potential therapeutic targets.
Area of Science:
- Immunology
- Dermatology
- Genomics
Background:
- Bullous pemphigoid (BP) causes significant cellular dysfunction in skin and circulation, but mechanisms are not fully understood.
- Understanding these cellular changes is crucial for developing effective treatments for BP.
Purpose of the Study:
- To investigate the functional changes in immune and non-immune cells in bullous pemphigoid patients using single-cell transcriptome analysis.
- To identify specific cell types and molecular pathways involved in BP pathogenesis and progression.
Main Methods:
- Single-cell transcriptome analysis of lesional and non-lesional skin, and blood samples from BP patients.
- Analysis of cellular pathways, immune cell signatures, and T cell receptor expansion.
Main Results:
- Lesional skin non-immune cells show upregulated metabolism, wound healing, immune activation, and migration pathways.
- Specific dendritic cells (LAMP3+DCs) and mast cells (VEGFA+) exhibit pro-inflammatory signatures in lesional skin.
- Blood B cells shift function during disease stages, and exhausted T cells show significant expansion linked to skin CD8+ T cells.
- Natural killer (NK) cell activity correlates with BP severity, with a balance between IFN-γ and amphiregulin (AREG) influencing keratinocyte apoptosis.
Conclusions:
- Single-cell analysis reveals distinct functional cellular shifts in bullous pemphigoid, impacting skin and blood compartments.
- Identification of specific cell populations (e.g., VEGFA+ mast cells, specific T and NK cells) and pathways provides insights into BP pathology.
- The balance between NK cell-derived AREG and IFN-γ is critical in BP, suggesting potential therapeutic modulation.
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