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Epicutaneous Application of Mannan Induces Psoriasis-like Inflammation in an Inbred Mouse Strain
Huimei Wu1,2, Kutty Selva Nandakumar2,3
1Department of Pharmacy, the Eighth Affiliated City Hospital of Guangzhou Medical University, The Eighth People's Hospital of Guangzhou, Guangzhou, China.
Abstract:
Mannan from yeast induces psoriasis-like inflammation in the skin of inbred mouse strains. Limitations of available models led us to develop a new psoriasis model with a rapid disease onset, severe disease course, short duration, and a simple and easy-to-induce protocol with much more practically convenient features and cost-benefits. Mannan-induced skin inflammation (MISI) is more severe than the classical imiquimod (IMQ)-induced skin inflammation (IISI), with characteristic features resembling human plaque psoriasis but with relatively fewer toxicity issues. Epicutaneous application of mannan (5 mg) in incomplete Freund's adjuvant or Vaseline induces severe psoriasis in BALB/c female mice. Psoriasis area and severity index (PASI) and histological evaluation of the skin could help assess the disease development. MISI mimics natural environmental factors affecting the skin relatively more closely than IISI. This disease model can be used to dissect inflammatory pathways in the skin, identify genetic and environmental factors affecting psoriasis, and test potential pharmacological agents or new combinations of available drugs for treatment before designing clinical trials. Key features • S. cerevisiae mannan induces psoriasis-like skin inflammation (MISI) when applied on the skin of inbred mice. • The MISI model has a rapid onset, severe disease, short duration, and simple and easy-to-induce protocol. • MISI is more severe than imiquimod-induced skin inflammation (IISI). • Female mice had a more severe disease than males in the MISI model, thereby allowing the study of sex-dependent disease mechanisms. • The MISI model identifies skin inflammatory pathways and genetic/environmental factors affecting psoriasis. • The MISI model can be used as a drug testing platform for potential pharmaceuticals to develop new therapeutics for psoriasis patients. • The MISI model can be used to explore the relative contribution of different pattern recognition receptors in the development and severity of psoriasis.
Insights
Yeast mannan rapidly induces severe psoriasis-like skin inflammation in mice. This new Mannan-Induced Skin Inflammation (MISI) model is more effective and less toxic than existing methods, offering a valuable tool for psoriasis research.
Area of Science:
- Dermatology
- Immunology
- Pathology
Background:
- Current psoriasis models have limitations in disease induction, severity, and duration.
- Developing a more practical and severe psoriasis model is crucial for research and drug development.
- Yeast-derived mannan offers a potential trigger for psoriasis-like inflammation.
Purpose of the Study:
- To develop and characterize a novel, rapid, and severe mouse model of psoriasis-like skin inflammation.
- To compare the efficacy and characteristics of the mannan-induced skin inflammation (MISI) model with the imiquimod-induced skin inflammation (IISI) model.
- To establish a cost-effective and convenient platform for studying psoriasis pathogenesis and testing therapeutics.
Main Methods:
- Epicutaneous application of Saccharomyces cerevisiae mannan (5 mg) in incomplete Freund's adjuvant or Vaseline on BALB/c female mice.
- Assessment of disease severity using Psoriasis Area and Severity Index (PASI) and histological evaluation.
- Comparison of MISI model with the classical imiquimod-induced skin inflammation (IISI) model.
Main Results:
- S. cerevisiae mannan induced severe psoriasis-like skin inflammation (MISI) with rapid onset and short duration.
- The MISI model exhibited greater severity than the IISI model, with fewer toxicity issues.
- Female mice showed more severe disease than males, enabling studies on sex-dependent mechanisms.
Conclusions:
- The MISI model provides a practical, severe, and rapidly induced platform for psoriasis research.
- MISI closely mimics human plaque psoriasis features and environmental factors, making it suitable for dissecting inflammatory pathways.
- This model serves as a valuable tool for identifying genetic/environmental factors and testing psoriasis therapeutics.
