Monocyte aggregates and intermediate (CD14++CD16+) cells that are associated with cardiac events are increased in human psoriatic blood and CD11b +Ly6C high cells and aggregates are increased in the KC-Tie2 psoriasiform mouse model (HUM1P.307)

Psoriasis confers an increased risk for developing and dying of cardiovascular disease (CVD). We found increased circulating CD14++CD16+ intermediate monocytes (IntMo), a cell type associated with increased cardiovascular risk, in psoriasis patients compared to healthy controls (N=42, 16.5%±2.7 vs. 11.9%±1.4, P=.056). Amnis imaging flow cytometry of the psoriatic IntMo cells revealed increased doublets and aggregates. Overall, CD14++ doublets are increased in psoriasis patients compared to controls (2.72%±0.58 vs. 1.09%±0.20; P=0.006). Murine psoriasiform skin models (KC-Tie2) exhibit increased vascular thrombosis and monocyte doublets, indicating a skin inflammation-driven process. KC-Tie2 mice are pro-thrombotic, develop aortic root vascular lesions, and have increased splenic CD11b +Ly6C high (Ly6Chigh) monocytes (33.8%±3.8, n=7) compared to controls (8.05%±0.55, n=9; P=0.0002), suggesting that chronic skin inflammation generates Ly6Chighcells which mediate vascular inflammation. KC-Tie2 mice also show an increase in Ly6Chighcells in skin-draining lymph nodes compared to controls (8.83%±0.77, n=18, vs. 1.94%±0.8, n=3, P=.002). Crossing IL-6 KO mice with KC-Tie2 decreases these splenic Ly6Chighcells, reverses thrombosis and aortic root vascular lesions, and eliminates skin inflammation. Psoriasis-driven accumulation, increase, and aggregation of monocytes in circulation suggests a novel mechanistic linkage between psoriatic skin disease and its CVD comorbidity.