Year: 2016
Type: article
Abstract: Psoriasis patients are at increased risk of heart attack and stroke and have elevated MRP8/14 levels that predict heart attack. The KC-Tie2 psoriasiform mouse model exhibits elevated MRP8/14 and is prothrombotic. Mrp14 –/– mice, in contrast, are protected from thrombosis, but, surprisingly, KC-Tie2x Mrp14 –/– mice remain prothrombotic. Treating KC-Tie2x Mrp14 –/– mice with anti–IL-23p19 antibodies reversed the skin inflammation, improved thrombosis, and decreased IL-6. In comparison, IL-6 deletion from KC-Tie2 animals improved thrombosis despite sustained skin inflammation, suggesting that thrombosis improvements following IL-23 inhibition occur secondary to IL-6 decreases. Psoriasis patient skin has elevated IL-6 and IL-6 receptor is present in human coronary atheroma, supporting a link between skin and distant vessel disease in patient tissue. Together, these results identify a critical role for skin-derived IL-6 linking skin inflammation with thrombosis, and shows that in the absence of IL-6 the connection between skin inflammation and thrombosis comorbidities is severed.
Source: JCI Insight
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,100
Awards: NIAMS: CORT (Psoriasis Center of Research Translation), G2312238953, NIAMS Core Center: Skin Diseases Research Center, Neurogenic inflammation and psoriasiform dermatitis, Inflammation in Vascular Injury and Repair, IL-17C mediated mechanisms of inflammation, Inflammation in Vascular Injury and Repair, Remote Inflammation and Atherothrombosis, Role of the Psoriasis Associated IL23R Risk Variants on Th17 Biology and Function, MRP-14, CD36 and Thrombosis, Role of IL-13 and the IL-13 Associated rs20541 Risk Variant in the Pathogenesis of Psoriasis, G9000146339
OpenAlex ID: W2560542209