Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 102, Issue 52, Pages 19057-19062Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0509736102
Keywords
autoimmune disease; CD11c; Tip-DC
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Funding
- NCRR NIH HHS [M01 RR000102, M01-RR00102] Funding Source: Medline
- NIAID NIH HHS [R01 AI049832, R01 AI-49572, R01 AI049572, AI-49832] Funding Source: Medline
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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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