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A Sex-Specific Anti-Inflammatory Role for p62 in Psoriasis-Like Disease
Kamil Mieczkowski1, Latifa Bakiri2, Johannes Griss3
1Laboratory Genes and Disease, Department of Dermatology, Medical University of Vienna, Vienna, Austria; Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
The Journal of Investigative Dermatology
|April 21, 2025
Summary
Psoriasis disease is worsened in males lacking the SQSTM1/p62 protein, revealing a sex-specific anti-inflammatory role for p62 in this chronic skin condition.
Area of Science:
- Dermatology
- Immunology
- Molecular Biology
Background:
- Psoriasis is a chronic inflammatory skin disease with complex immune and epidermal cell interactions.
- Psoriasis often presents with systemic issues like psoriatic arthritis.
- SQSTM1/p62, a protein regulating autophagy, differentiation, and inflammation, is elevated in psoriatic skin.
Purpose of the Study:
- To investigate the role of SQSTM1/p62 in psoriasis-like phenotypes.
- To analyze the impact of p62 deficiency on skin and joint inflammation in a mouse model.
Main Methods:
- Utilized a mouse model with inducible epidermal inactivation of c-Jun and JunB (DKO*).
- Crossed DKO* mice with p62 knockout mice (p62-/-) to create DKO* p62-/- mice.
- Analyzed skin and joint phenotypes, focusing on sex-specific differences.
Main Results:
- Male DKO* p62-/- mice exhibited aggravated skin and joint disease compared to other groups.
- Skin of male DKO* p62-/- mice showed epidermal thickening, impaired keratinocyte differentiation, increased immune cell infiltration, and elevated CXCL1.
- Increased androgen receptor signaling, inflammasome activity, and KEAP1/NRF2 pathway activation were observed in male DKO* p62-/- mice skin.
Conclusions:
- SQSTM1/p62 plays a sex-specific anti-inflammatory role in psoriasis-like disease.
- Androgen signaling and inflammasome activation contribute to disease exacerbation in males lacking p62.
- Findings suggest p62's role may have clinical relevance for psoriasis treatment.
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