cytokine releaseden, dritic cel, ldisease activity, histopathology, keratinocyte, Langerhans cell, skin inflammation
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 a, 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.
Lowes, M. A., F. Chamian, M. V. Abello, J. Fuentes-Duculan, S. -L Lin, R. Nussbaum, I. Novitskaya, et al. 2005. "Increase in TNF-α and Inducible Nitric Oxide Synthase-Expressing Dendritic Cells in Psoriasis and Reduction with Efalizumab (Anti-CD11a)." Proceedings of the National Academy of Sciences of the United States of America 102 (52): 19057-19062