Decoding autoimmune bullous diseases from single-cell RNA-seq and future directions.

Area of Science:

• Immunodermatology
• Molecular Biology
• Genomics

Background:

• Autoimmune bullous diseases (AIBDs) involve autoantibody-mediated damage to skin and mucous membranes.
• Shared immune mechanisms disrupt epithelial integrity, but cellular dynamics and drivers are unclear, limiting targeted therapies.

Purpose of the Study:

• To review single-cell RNA sequencing (scRNA-seq) findings in AIBDs, focusing on pemphigus and bullous pemphigoid.
• To highlight how scRNA-seq elucidates disease heterogeneity and molecular mechanisms.

Main Methods:

• Comprehensive literature review of scRNA-seq studies (1978-2024) on AIBDs.
• Analysis of findings related to cellular subpopulations, cytokine networks, and intercellular crosstalk.

Main Results:

• scRNA-seq has identified distinct cell subpopulations in AIBDs.
• Dysregulated cytokine/chemokine networks and pathogenic intercellular crosstalk have been revealed.
• scRNA-seq advances understanding of AIBD pathophysiology and cellular heterogeneity.

Conclusions:

• scRNA-seq offers insights into AIBD heterogeneity and immune crosstalk.
• Limitations include specimen scarcity, spatial resolution, and unvalidated signatures.
• Future directions involve multi-omics, spatial transcriptomics, and AI for novel therapeutic targets and precision medicine.