Increase in TNF-alpha and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a) |
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| Authors: | Lowes Michelle A Chamian Francesca Abello Maria Veronica Fuentes-Duculan Judilyn Lin Shao-Lee Nussbaum Rachel Novitskaya Inna Carbonaro Henrietta Cardinale Irma Kikuchi Toyoko Gilleaudeau Patricia Sullivan-Whalen Mary Wittkowski Knut M Papp Kim Garovoy Marvin Dummer Wolfgang Steinman Ralph M Krueger James G |
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| Affiliation: | Laboratory for Investigative Dermatology and Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021, USA. |
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| 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. |
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