TWEAK mediates inflammation in experimental atopic dermatitis and psoriasis

Area of Science:

• Immunology
• Dermatology
• Molecular Biology

Background:

• Atopic dermatitis (AD) and psoriasis involve distinct T helper type 2 (Th2) and T helper type 17 (Th17) immune responses, respectively.
• The role of shared molecular mediators in both AD and psoriasis remains an area of investigation.

Purpose of the Study:

• To investigate the role of Tumor Necrosis Factor Superfamily Molecule 12 (TNFSF12), also known as TWEAK, in the pathogenesis of atopic dermatitis and psoriasis.
• To determine if TWEAK acts as a critical contributor to skin inflammation in both diseases.

Main Methods:

• Studied TWEAK-deficient mice to assess the maintenance of AD-specific Th2 and psoriasis-specific Th17 cells.
• Analyzed the expression of key chemokines and cytokines (CCL17, TSLP, CCL20, IL-19) in skin samples.
• Investigated the TWEAK receptor, Fn14, expression in keratinocytes and dermal fibroblasts.
• Administered recombinant TWEAK to naive mice to induce skin inflammation.

Main Results:

• TWEAK deficiency led to defective maintenance of AD-specific Th2 and psoriasis-specific Th17 cells in the skin.
• Impaired expression of disease-characteristic chemokines and cytokines was observed in TWEAK-deficient mice.
• TWEAK, acting through its receptor Fn14, induced cytokines and chemokines, alone and synergistically with IL-13 and IL-17.
• Subcutaneous TWEAK injection in naive mice induced cutaneous inflammation with features of both AD and psoriasis.

Conclusions:

• TWEAK is a critical contributor to skin inflammation in both atopic dermatitis and psoriasis.
• TWEAK and its signaling pathway represent a potential therapeutic target for managing AD and psoriasis.