Psoriasis-Associated Late Cornified Envelope (LCE) Proteins Have Antibacterial Activity

Area of Science:

• Dermatology
• Genetics
• Immunology

Background:

• Epidermal keratinocytes produce proteins crucial for skin barrier function and innate immunity.
• Late Cornified Envelope (LCE) genes encode 18 epidermal proteins with largely unknown functions.
• LCE3B/C deletion is a known psoriasis risk factor, interacting with HLA-C*06.

Purpose of the Study:

• To investigate the function of LCE3 proteins.
• To explore the link between LCE3B/C deletion and increased LCE3A expression.
• To determine the role of LCE3 proteins in epidermal host defense and psoriasis pathogenesis.

Main Methods:

• Quantitative trait locus analysis using RNA-seq data from human skin.
• Validation in a 3D skin model with primary keratinocytes.
• Functional assays to assess antimicrobial activity and skin barrier function.

Main Results:

• LCE3B/C deletion correlated with significantly increased LCE3A expression.
• LCE3 proteins, especially LCE3A, demonstrated defensin-like antimicrobial activity against various bacteria.
• No genotype-dependent impact on physical skin barrier function was observed.

Conclusions:

• LCE3 proteins possess antimicrobial properties, contributing to epidermal innate host defense.
• Increased LCE3A expression due to LCE3B/C deletion may underlie its role in psoriasis risk.
• This study elucidates a novel function for LCE3 proteins in skin immunity.