Murine models of psoriasis and their usefulness for drug discovery

ABSTRACT

Introduction: Psoriasis is an autoimmune skin disease characterized by red plaques with silver or white multilayered scales with a thickened acanthotic epidermis. Using mouse models of cutaneous inflammation, IL-23/Th17 was identified to have a potential key role in psoriasis. New treatments to slow this inflammatory skin disorder are urgently needed. To aid their discovery, a psoriasis animal model mimicking human psoriasis is urgently needed for their early preclinical evaluation.

Areas covered: The authors review animal models of psoriasis and analyze the features and molecular mechanisms involved in these mouse models. The application of various mouse models of psoriasis for drug discovery and development has also been reviewed and the possible molecular targets in psoriasis for future anti-psoriatic drug design is discussed.

Expert opinion: So far, it has been difficult to create an animal model that exactly simulates a human disease or condition. The xenotransplantation model is regarded as the closest to incorporating the complete genetic, phenotypic, and immunopathogenic processes of psoriasis. However, the imiquimod (IMQ)-induced model is the most prevalent among psoriatic mouse models due to its ease of use, convenience, and low cost. Further efforts to develop psoriasis-like skin models in mice are needed for the study and treatment of this complex disease.

KEYWORDS:

• Psoriasis
• animal model
• murine
• IL-23/Th17
• drug development

Article highlights

• Crosstalk between activated fibroblasts, infiltrating T cells and epidermal keratinocytes enhances the inflammatory process and causes epidermal proliferation in psoriasis.

• The research on the application of animal models of psoriasis has shown dramatically increasing numbers over the past 2 decades.

• The psoriasis-like animal models are employed for testing the therapeutic efficiency of several approved IL-23/IL-17 antagonists and small amolecules.

• The animal models and their potential value for psoriasis research include spontaneous, genetically engineered, xenotransplantation, and directly induced approaches.

• The xenotransplantation model is regarded as the closest to incorporating the complete genetic, phenotypic, and immunopathogenic processes of psoriasis. However, the imiquimod (IMQ)-induced model is the most prevalence of the use of psoriatic mouse model, due to easy-to-use, convenient, and cheap.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors are grateful for the financial support from Chang Gung Memorial Hospital (CMRPD1F0331-3).