Increase in TNF-α and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a)

• DOI: 10.1073/pnas.0509736102
• Publication Date: 2005-12-27T17:52:37Z
• Authors: Michelle A. Lowes; Francesca Chamian; Maria Veronica Ab...; Judilyn Fuentes-D...; Shao-Lee Lin; Rachel Nussbaum; Inna Novitskaya; Henrietta Carbonaro; Irma Cardinale; Toyoko Kikuchi; Patricia Gilleaudeau; Mary Sullivan-Whalen; Knut M. Wittkowski; Kim Papp; Marvin Garovoy; Wolfgang Dummer; Ralph M. Steinman; James G. Krueger
• Keywords: Inflammation; 0301 basic medicine; Membrane Glycoproteins; Antibodies, Monoclonal; Immunoglobulins; Nitric Oxide Synthase Type II; Cell Separation; Dendritic Cells; HLA-DR Antigens; Antibodies, Monoclonal, Humanized; Flow Cytometry; Immunohistochemistry; Lysosomal Membrane Proteins; CD11c Antigen; 03 medical and health sciences; Microscopy, Fluorescence; Antigens, CD; Humans; Psoriasis; B7-2 Antigen; RNA, Messenger; CD40 Antigens

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-α 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-α production, and can be an important target for suppressive therapies.