title: 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 for 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(++)CD16(-) 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(++)CD16(-)) 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 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.
authors.affiliation: Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106; Department of Pathology, Case Western Reserve University, Cleveland, OH 44106;
authors.forename: Jackelyn B
authors.initials: JB
authors.lastname: Golden
authors.affiliation: Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106;
authors.forename: Sarah G
authors.initials: SG
authors.lastname: Groft
authors.affiliation: Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106;
authors.forename: Michael V
authors.initials: MV
authors.lastname: Squeri
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106;
authors.forename: Sara M
authors.initials: SM
authors.lastname: Debanne
authors.affiliation: Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106; Murdough Family Center for Psoriasis, Cleveland, OH 44106; University Hospitals Case Medical Center, Cleveland, OH 44106; and.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Ward
authors.affiliation: Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106; Murdough Family Center for Psoriasis, Cleveland, OH 44106; University Hospitals Case Medical Center, Cleveland, OH 44106; and.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: McCormick
authors.affiliation: Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106; Department of Pathology, Case Western Reserve University, Cleveland, OH 44106; Murdough Family Center for Psoriasis, Cleveland, OH 44106; University Hospitals Case Medical Center, Cleveland, OH 44106; and Veterans Affairs Medical Center, Cleveland, OH 44106 kdc@case.edu.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Cooper
mesh_terms: D000328:Adult; D000818:Animals; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D002449:Cell Aggregation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D002908:Chronic Disease; D018920:Coculture Techniques; D003872:Dermatitis / Q000097:blood / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008297:Male; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D011565:Psoriasis / Q000097:blood / Q000235:genetics / Q000276:immunology*; D042787:Receptor, TIE-2 / Q000235:genetics / Q000378:metabolism; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome / Q000276:immunology*; D055815:Young Adult
chemical_list: D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D042787:Receptor, TIE-2