Single-cell transcriptomics and spatial validation reveal dysfunction of keratinocytes and NK cells driving acne...

Area of Science:

• Dermatology and immunology
• Molecular and cellular biology
• Transcriptomics and spatial biology

Background:

• Acne is a common inflammatory skin condition with poorly understood cellular and molecular drivers.
• Existing research lacks detailed insights into the dynamic interplay between skin barrier cells and immune cells during acne development.

Purpose of the Study:

• To elucidate the cellular composition and functional states in healthy, mild, and severe acne skin.
• To identify key molecular pathways and cellular interactions contributing to acne pathogenesis.
• To propose a novel pathological model for acne and explore potential therapeutic strategies.

Main Methods:

• Integration of single-cell transcriptomics and spatial immunofluorescence.
• Analysis of cellular states, functional pathways (e.g., TNF, chemokine signaling, NK cell cytotoxicity, Wnt/p53-apoptosis), and disease severity.
• Validation of findings through immunofluorescence.

Main Results:

• Keratinocytes shift from barrier defense in mild acne to abnormal differentiation and pathological keratinization in severe acne.
• Natural killer (NK) cells initially promote inflammation but later undergo exhaustion and apoptosis, contributing to an 'immune-barrier imbalance'.
• Disease severity correlates strongly with TNF, chemokine signaling, NK cell cytotoxicity, and Wnt/p53-apoptosis pathways.

Conclusions:

• A novel 'dual immune-barrier imbalance' model explains acne progression.
• Findings support 'immune-barrier co-regulation' as a therapeutic strategy for acne.
• This research provides a foundation for early diagnosis and precision interventions in acne.