Sequestosome 1/p62 enhances chronic skin inflammation

Area of Science:

• Dermatology
• Immunology
• Molecular Biology

Background:

• The molecular mechanisms underlying inflammation and epidermal thickening in atopic dermatitis (AD) remain unclear.
• Sequestosome 1/p62 is an adapter protein involved in regulating inflammatory and mTOR signaling pathways.

Purpose of the Study:

• To investigate the role of p62 in the skin and systemic features of an AD-like mouse model.

Main Methods:

• AD-like skin lesions were induced by deleting JunB/AP-1 in epidermal keratinocytes (JunB^Δep).
• The impact of p62 on pathological changes was assessed by inactivating p62 in JunB^Δepp62^-/- double knockout mice.

Main Results:

• p62 expression was elevated in AD-like skin lesions, similar to AD and psoriasis.
• Inactivating p62 significantly reduced keratinocyte differentiation defects, epidermal thickening, immune cell infiltration, and lesion development.
• p62 inactivation decreased serum IgE and modulated mTOR and NF-κB signaling in the skin.

Conclusions:

• This study provides the first in vivo evidence of p62's pro-inflammatory role in skin.
• p62-dependent signaling pathways represent potential therapeutic targets for managing skin manifestations of AD and psoriasis.