Long-Term and Clinically Relevant Full-Thickness Human Skin Equivalent for Psoriasis

Area of Science:

• Biotechnology
• Dermatology
• Inflammation Research

Background:

• Psoriasis is a chronic, immune-mediated skin disease with no cure.
• Current preclinical models like animal testing and simple cell cultures have limitations in fully recapitulating psoriasis.
• Existing 3D skin equivalents lack the long-term stability needed for complex disease modeling and drug testing.

Purpose of the Study:

• To develop a stable, scaffold-free, full-thickness human skin equivalent (HSE) model.
• To establish a psoriasis-like phenotype in the HSE model using recombinant human interleukin 17A (rhIL-17A).
• To evaluate the efficacy of the anti-IL-17A antibody secukinumab in treating the induced psoriatic phenotype in the HSE model.

Main Methods:

• Fabrication of HSEs using a cell coating technique with layer-by-layer assembly for enhanced stability (up to 49 days).
• Induction of a psoriatic phenotype by stimulating HSEs with rhIL-17A.
• Treatment of rhIL-17A-stimulated HSEs with the anti-IL-17A antibody secukinumab.
• Analysis of gene expression changes using microarray and RT-PCR, followed by gene ontology analysis.

Main Results:

• rhIL-17A stimulation led to downregulation of keratinocyte differentiation markers and upregulation of pro-inflammatory cytokines and chemokines in HSEs.
• Treatment with secukinumab effectively reversed the rhIL-17A-induced gene expression changes.
• Gene ontology analysis confirmed the pro-inflammatory and chemotactic effects of rhIL-17A and the therapeutic impact of secukinumab.

Conclusions:

• The developed scaffold-free HSE model offers long-term stability and accurately replicates key molecular aspects of psoriasis.
• This HSE model serves as a viable alternative to animal testing and ex vivo skin explants for studying psoriasis pathogenesis.
• The model demonstrates the molecular efficacy of anti-IL-17A therapy, paving the way for advanced preclinical drug evaluation.