IL-12 protects from psoriasiform skin inflammation

Area of Science:

• Immunology
• Dermatology
• Molecular Biology

Background:

• Interleukin-12/23 (IL-12/23) p40 subunit neutralization is a breakthrough therapy for moderate to severe psoriasis.
• Anti-p40 therapies target both IL-12 and IL-23, impacting type 1 immunity and IL-23-driven inflammation.

Purpose of the Study:

• To dissect the individual roles of IL-12 and IL-23 in psoriasis pathogenesis.
• To evaluate the therapeutic effect of co-targeting IL-12 and IL-23 in psoriasis models.

Main Methods:

• Utilized a preclinical model of psoriatic plaque formation.
• Investigated cytokine signaling pathways in keratinocytes and immune cells.

Main Results:

• IL-12, unlike IL-23, demonstrated a regulatory function by inhibiting IL-17-committed γδT17 cell infiltration.
• IL-12 receptor signaling in keratinocytes initiated a protective transcriptional program limiting skin inflammation.

Conclusions:

• Collateral targeting of IL-12 by anti-p40 monoclonal antibodies may be counterproductive in psoriasis therapy.
• Understanding the distinct roles of IL-12 and IL-23 is crucial for optimizing psoriasis treatment strategies.