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


ABSTRACT: Psoriasis patients experience chronic systemic skin inflammation and develop cardiovascular comorbidities that shorten their lifespan. Whether cardiovascular disease is improved by treatment with current biologics that target disease-specific pathways is unclear. KC-Tie2 mice develop psoriasiform skin inflammation with increases in IL-23 and IL-17A and proinflammatory monocytosis and neutrophilia that precedes development of carotid artery thrombus formation. To examine whether targeted blockade of IL-23 or IL-17A in KC-Tie2 psoriasis mice improves cardiovascular outcomes, mice were treated systemically for 6 weeks with antibodies targeting IL-17A, IL-17RA, IL-12/23p40, or IL-23p19. Skin inflammation; thrombosis clotting times; and percentage of splenic monocytes, neutrophils, and CD4 T cells were examined. Skin inflammation significantly improved in KC-Tie2 mice treated with each of the antibodies targeting IL-23, IL-17A, or IL-17RA, consistent with clinical efficacy observed in psoriasis patients. The time to occlusive thrombus formation lengthened in these mice and correlated with attenuated acanthosis. This decrease in skin inflammation paralleled decreases in splenic neutrophils (CD11b+Ly6G+) but not monocytes (CD11b+Ly6Chigh) or T cells (CD4+). Our data show that targeted inhibition of IL-23 or IL-17A improves psoriasis-like skin disease and also improves cardiovascular disease in mice.

SUBMITTER: Li Y 

PROVIDER: S-EPMC6693345 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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

Li Yumeng Y   Golden Jackelyn B JB   Camhi Maya I MI   Zhang Xiufen X   Fritz Yi Y   Diaconu Doina D   Ivanco Tammy L TL   Simon Daniel I DI   Kikly Kristine K   McCormick Thomas S TS   Wang Yunmei Y   Ward Nicole L NL  

The Journal of investigative dermatology 20170923 2


Psoriasis patients experience chronic systemic skin inflammation and develop cardiovascular comorbidities that shorten their lifespan. Whether cardiovascular disease is improved by treatment with current biologics that target disease-specific pathways is unclear. KC-Tie2 mice develop psoriasiform skin inflammation with increases in IL-23 and IL-17A and proinflammatory monocytosis and neutrophilia that precedes development of carotid artery thrombus formation. To examine whether targeted blockade  ...[more]

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