TY - JOUR
T1 - Increase in TNF-α and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a)
AU - Lowes, Michelle A.
AU - Chamian, Francesca
AU - Abello, Maria Veronica
AU - Fuentes-Duculan, Judilyn
AU - Lin, Shao Lee
AU - Nussbaum, Rachel
AU - Novitskaya, Inna
AU - Carbonaro, Henrietta
AU - Cardinale, Irma
AU - Kikuchi, Toyoko
AU - Gilleaudeau, Patricia
AU - Sullivan-Whalen, Mary
AU - Wittkowski, Knut M.
AU - Papp, Kim
AU - Garovoy, Marvin
AU - Dummer, Wolfgang
AU - Steinman, Ralph M.
AU - Krueger, James G.
PY - 2005/12/27
Y1 - 2005/12/27
N2 - 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.
AB - 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.
KW - Autoimmune disease
KW - CD11c
KW - Tip-DC
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U2 - 10.1073/pnas.0509736102
DO - 10.1073/pnas.0509736102
M3 - Article
C2 - 16380428
AN - SCOPUS:30044435436
SN - 0027-8424
VL - 102
SP - 19057
EP - 19062
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 52
ER -