Protection from Psoriasis-Related Thrombosis after Inhibition of IL-23 or IL-17A

Area of Science:

• Immunodermatology
• Cardiovascular Medicine
• Translational Research

Background:

• Psoriasis is a chronic inflammatory skin disease linked to cardiovascular comorbidities.
• Current biologic treatments targeting specific pathways show efficacy in psoriasis but their cardiovascular benefits remain unclear.
• KC-Tie2 mice model psoriasiform skin inflammation, elevated IL-23/IL-17A, and precede carotid artery thrombus formation.

Purpose of the Study:

• To investigate if blocking IL-23 or IL-17A pathways improves cardiovascular outcomes in a mouse model of psoriasis.
• To assess the impact of targeted biologic therapies on skin inflammation and thrombosis in KC-Tie2 mice.

Main Methods:

• KC-Tie2 mice with psoriasiform skin inflammation were treated with antibodies targeting IL-17A, IL-17RA, IL-12/23p40, or IL-23p19 for 6 weeks.
• Evaluated skin inflammation, carotid artery thrombosis clotting times, and immune cell populations (monocytes, neutrophils, CD4 T cells) in the spleen.
• Correlated skin inflammation severity with cardiovascular outcomes.

Main Results:

• Systemic treatment with antibodies targeting IL-23, IL-17A, or IL-17RA significantly reduced skin inflammation in KC-Tie2 mice.
• These treatments also increased the time to occlusive thrombus formation, indicating improved cardiovascular outcomes.
• Reduced skin inflammation correlated with decreased splenic neutrophils, but not monocytes or CD4 T cells.

Conclusions:

• Targeted inhibition of IL-23 or IL-17A effectively ameliorates psoriasis-like skin disease in mice.
• These targeted therapies demonstrate a positive impact on cardiovascular disease parameters in the studied mouse model.
• The findings suggest that IL-23 and IL-17A pathways are critical links between psoriasis and cardiovascular comorbidities.