Chronic Psoriatic Skin Inflammation Leads to Increased Monocyte Adhesion and Aggregation

Abstract

Psoriasis patients exhibit an increased risk of death by cardiovascular disease (CVD) and have elevated levels of circulating intermediate (CD14++CD16+) monocytes. This elevation could represent evidence of monocyte dysfunction in psoriasis patients at risk of CVD, as increases in circulating CD14++CD16+ monocytes are predictive of myocardial infarction and death. An elevation in the CD14++CD16+ cell population has been previously reported in patients with psoriatic disease, which has been confirmed in the cohort of our human psoriasis patients. CD16 expression was induced in CD14++CD16neg classical monocytes following plastic adhesion, which also elicited enhanced β2 but not β1 integrin surface expression, suggesting increased adhesive capacity. Indeed, we found that psoriasis patients have increased monocyte aggregation among circulating PBMCs which is recapitulated in the KC-Tie2 murine model of psoriasis. Visualization of human monocyte aggregates using imaging cytometry revealed that classical CD14++CD16neg monocytes are the predominant cell type participating in these aggregate pairs. Many of these pairs also included CD16+ monocytes, which could account for apparent elevations of intermediate monocytes. Additionally, intermediate monocytes and monocyte aggregates were the predominant cell type to adhere to TNF-α and IL-17A-stimulated dermal endothelium. Ingenuity Pathway Analysis (IPA) demonstrated that monocyte aggregates have a distinct transcriptional profile from singlet monocytes and monocytes following plastic adhesion, suggesting that circulating monocyte responses to aggregation are not fully accounted for by homotypic adhesion, and that further factors influence their functionality.

Psoriasis and Psoriatic Arthritis Cardiovascular Disease Endotypes Identified by Red Blood Cell Distribution Width and Mean Platelet Volume

“…Prior psoriasis studies on markers of local inflammation which are associated with an increased risk of CVD include myeloperoxidase, a pro-inflammatory heme protein released by myeloid cells (most likely released into circulation by MPO-producing skin-infiltrating myeloid cells), and resistin, an adipose-tissue derived hormone (most likely from adipose tissue subjacent to psoriasis plaques) [21][22][23][24][25]. In addition, we and others demonstrated that myeloid cells are altered in psoriasis patients, where the number of monocyte-derived suppressor cells (MDSCs) and intermediate (CD14 + CD16 + ) monocytes are increased in psoriasis patients, potentially as a result of similarly disordered myeloid cell release [24,[26][27][28][29][30][31][32].…”

Interleukin 6 regulates psoriasiform inflammation–associated thrombosis

“…We previously reported increases in proinflammatory CD11b + Ly6C hi monocytes in KC-Tie2 mice (17,63) that precede the development of aortic root inflammation and shortened arterial thrombosis times, leading us to speculate that monocytes may participate in the thrombus formation. In mice with lengthened (protected) thrombosis clotting times (KC-Tie2xIL-6 -/-), we observed modest decreases in proinflammatory CD11b + Ly6C hi monocytes; however, these decreases occurred concomitantly with much larger reductions in circulating platelets and neutrophils, suggesting perhaps a more critical role for these cells in the promotion of thrombosis versus the monocytes.…”

Evaluation of Antipsoriatic Activity of Aqueous Extract of Brassica Oleracea Var. Capitata and Ethanolic Extract of Mentha Spicata Leaves on Imiquimod-Induced Psoriasis-Like Dermatitis

“…Eosinophils provide inflammatory signals that accelerate the pathogenesis of psoriasis [26]. High levels of monocytes indicate autoimmune disorders [27]. In auto-immune diseases, the immune system attacks and destroys RBC, platelets [28] and platelets may get trapped in the spleen [29].…”