title: Increase in TNF-alpha and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a).
abstract: We find that CD11c(+) cells with many markers of dendritic cells (DCs) are a major cell type in the skin lesions of psoriasis. These CD11c(+) cells, which are evident in both epidermis and dermis, are the sites for the expression of two mediators of inflammation, inducible nitric oxide synthase (iNOS) and TNF-alpha in diseased skin. These cells express HLA-DR, CD40, and CD86, lack the Langerin and CD14 markers of Langerhans cells and monocytes, respectively, and to a significant extent express the DC maturation markers DC-LAMP and CD83. Treatment of psoriasis with efalizumab (anti-CD11a, Raptiva) strongly reduces infiltration by these DCs in patients responding to this agent. Disease activity after therapy was more related to DC infiltrates and iNOS mRNA levels than T cell infiltrates, and CD11c(+) cells responded more quickly to therapy than epidermal keratinocytes. Our results suggest that a type of DC, which resembles murine "Tip-DCs" that can accumulate during infection, has proinflammatory effects in psoriasis through nitric oxide and TNF-alpha production, and can be an important target for suppressive therapies.
authors.affiliation: Laboratory for Investigative Dermatology and Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021, USA.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Lowes
authors.forename: Francesca
authors.initials: F
authors.lastname: Chamian
authors.forename: Maria Veronica
authors.initials: MV
authors.lastname: Abello
authors.forename: Judilyn
authors.initials: J
authors.lastname: Fuentes-Duculan
authors.forename: Shao-Lee
authors.initials: SL
authors.lastname: Lin
authors.forename: Rachel
authors.initials: R
authors.lastname: Nussbaum
authors.forename: Inna
authors.initials: I
authors.lastname: Novitskaya
authors.forename: Henrietta
authors.initials: H
authors.lastname: Carbonaro
authors.forename: Irma
authors.initials: I
authors.lastname: Cardinale
authors.forename: Toyoko
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Patricia
authors.initials: P
authors.lastname: Gilleaudeau
authors.forename: Mary
authors.initials: M
authors.lastname: Sullivan-Whalen
authors.forename: Knut M
authors.initials: KM
authors.lastname: Wittkowski
authors.forename: Kim
authors.initials: K
authors.lastname: Papp
authors.forename: Marvin
authors.initials: M
authors.lastname: Garovoy
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dummer
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Steinman
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000096:biosynthesis; D051940:B7-2 Antigen / Q000096:biosynthesis; D039521:CD11c Antigen / Q000096:biosynthesis; D019013:CD40 Antigens / Q000096:biosynthesis; D002469:Cell Separation; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D007150:Immunohistochemistry; D007249:Inflammation; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008856:Microscopy, Fluorescence; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism / Q000502:physiology*; D011565:Psoriasis / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D000097802:CD83 Antigen
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D051940:B7-2 Antigen; D039521:CD11c Antigen; D019013:CD40 Antigens; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000097802:CD83 Antigen; C472181:efalizumab