1. Increase in TNF-alpha and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a).
- Author
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Lowes MA, Chamian F, Abello MV, Fuentes-Duculan J, Lin SL, Nussbaum R, Novitskaya I, Carbonaro H, Cardinale I, Kikuchi T, Gilleaudeau P, Sullivan-Whalen M, Wittkowski KM, Papp K, Garovoy M, Dummer W, Steinman RM, and Krueger JG more...
- Subjects
- Antibodies, Monoclonal, Humanized, Antigens, CD biosynthesis, B7-2 Antigen biosynthesis, CD11c Antigen biosynthesis, CD40 Antigens biosynthesis, Cell Separation, Dendritic Cells metabolism, Flow Cytometry, HLA-DR Antigens metabolism, Humans, Immunoglobulins biosynthesis, Immunohistochemistry, Inflammation, Lysosomal Membrane Proteins metabolism, Membrane Glycoproteins biosynthesis, Microscopy, Fluorescence, Nitric Oxide Synthase Type II metabolism, Psoriasis metabolism, RNA, Messenger metabolism, Time Factors, CD83 Antigen, Antibodies, Monoclonal pharmacology, Dendritic Cells cytology, Nitric Oxide Synthase Type II physiology, Psoriasis pathology, Tumor Necrosis Factor-alpha physiology
- 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. more...
- Published
- 2005
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