1. Increase in TNF-alpha and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a)
- Author
-
Judilyn Fuentes-Duculan, Francesca Chamian, Mary Sullivan-Whalen, Patricia Gilleaudeau, Inna Novitskaya, Michelle A. Lowes, Toyoko Kikuchi, Rachel Nussbaum, Marvin Garovoy, Wolfgang Dummer, Maria Veronica Abello, Shao Lee Lin, Henrietta Carbonaro, Irma Cardinale, Ralph M. Steinman, James G. Krueger, Knut M. Wittkowski, and Kim A. Papp
- Subjects
Langerhans cell ,Time Factors ,Langerin ,T cell ,CD14 ,Immunoglobulins ,Nitric Oxide Synthase Type II ,chemical and pharmacologic phenomena ,CD11a ,Cell Separation ,Antibodies, Monoclonal, Humanized ,Antigens, CD ,Psoriasis ,medicine ,Humans ,RNA, Messenger ,CD40 Antigens ,Inflammation ,Multidisciplinary ,CD40 ,Membrane Glycoproteins ,biology ,integumentary system ,Tumor Necrosis Factor-alpha ,Antibodies, Monoclonal ,Lysosome-Associated Membrane Glycoproteins ,hemic and immune systems ,Dendritic Cells ,HLA-DR Antigens ,Biological Sciences ,medicine.disease ,Flow Cytometry ,Immunohistochemistry ,CD11c Antigen ,medicine.anatomical_structure ,Microscopy, Fluorescence ,Immunology ,biology.protein ,Tumor necrosis factor alpha ,B7-2 Antigen - 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-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.
- Published
- 2005