title: Increased, but Functionally Impaired, CD14(+) HLA-DR(-/low) Myeloid-Derived Suppressor Cells in Psoriasis: A Mechanism of Dysregulated T Cells.
abstract: The clinical extent of psoriasis pathology is regulated in part by defects in immune networks, including a defect in the suppressive actions of regulatory T cells. Recently, CD14(+) HLA-DR(-/low) monocytic myeloid-derived suppressor cells (Mo-MDSCs) have been shown to suppress T-cell activation as one of their suppressive mechanisms. However, little is known about the role of Mo-MDSCs and their functional relationship to T-cell suppression in relation to human chronic immune-mediated inflammatory diseases, including psoriasis. Despite psoriasis being a hyperinflammatory condition, Mo-MDSCs were elevated in psoriatic patient peripheral blood mononuclear cells compared to nonpsoriatic healthy controls (2.6% vs. 0.9%, P < 0.002). Freshly isolated psoriatic Mo-MDSCs directly suppressed CD8 T-cell proliferation less efficiently than healthy control Mo-MDSCs. In addition, psoriatic Mo-MDSCs expressed reduced surface expression of programmed cell death protein 1 compared to healthy controls. Additional in vitro assays also demonstrated that psoriatic and control Mo-MDSCs both induce regulatory T-cell conversion from naïve T effector cells, but, importantly, the regulatory T cells induced by psoriatic Mo-MDSCs displayed decreased suppressive functionality. These results suggest that aberrations in psoriatic Mo-MDSCs prevent proper suppression of effector T-cell expansion and hamper the immune system's ability to correctly self-regulate.
authors.affiliation: Department of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Soler
authors.affiliation: Department of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Young
authors.affiliation: Department of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Lori
authors.initials: L
authors.lastname: Fiessinger
authors.affiliation: Department of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Galimberti
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Debanne
authors.affiliation: Department of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Groft
authors.affiliation: Department of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA; The Murdough Family Center for Psoriasis, Cleveland, Ohio, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: McCormick
authors.affiliation: Department of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA; The Murdough Family Center for Psoriasis, Cleveland, Ohio, USA; University Hospitals Case Medical Center and VA Medical Center, Cleveland, Ohio, USA. Electronic address: kdc@case.edu.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Cooper
mesh_terms: D000328:Adult; D000368:Aged; D060890:B7-H1 Antigen / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D016753:Interleukin-10 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000166:cytology; D018384:Oxidative Stress; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D011565:Psoriasis / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology; D055815:Young Adult
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D006684:HLA-DR Antigens; C508609:IL10 protein, human; D018950:Lipopolysaccharide Receptors; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D017382:Reactive Oxygen Species; D016753:Interleukin-10