Reevaluating the Imiquimod Model: A Barrier to Translational Progress in Psoriasis

Area of Science:

• Dermatology
• Immunology
• Translational Medicine

Background:

• The imiquimod (IMQ) mouse model has been widely used for psoriasis research.
• Concerns exist regarding its relevance to chronic human psoriasis, particularly adaptive immunity.
• Previous critiques highlighted limitations, yet the model's use persists.

Purpose of the Study:

• To re-evaluate the limitations of the IMQ mouse model in psoriasis research.
• To assess its disconnect from human disease pathophysiology.
• To advocate for the development of more relevant research models.

Main Methods:

• Review of existing literature and critiques of the IMQ model.
• Analysis of methodological inconsistencies and transcriptomic data.
• Comparison of IMQ-induced inflammation with human psoriasis characteristics.

Main Results:

• The IMQ model primarily reflects acute, innate inflammation, not chronic adaptive immunity seen in psoriasis.
• Significant methodological drift and inconsistencies in model application have occurred.
• Transcriptomic analysis shows poor overlap between IMQ model data and human psoriasis.
• The model offers an illusion of mechanistic discovery rather than true insight.

Conclusions:

• The continued reliance on the IMQ model hinders progress in understanding chronic psoriasis.
• Methodological drift and poor biological relevance limit its utility.
• Advancement in psoriasis research requires transitioning to more faithful disease models.
• Future efforts should focus on systems that accurately capture the complexity of human psoriasis.