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

Michelle A. Lowes, Francesca Chamian, Maria Veronica Abello, Judilyn Fuentes-Duculan, 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

Research output: Contribution to journalArticle

334 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)19057-19062
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number52
DOIs
StatePublished - Dec 27 2005
Externally publishedYes

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Nitric Oxide Synthase Type II
Psoriasis
Dendritic Cells
Inflammation Mediators
Langerhans Cells
HLA-DR Antigens
Therapeutics
Dermis
efalizumab
Keratinocytes
Skin Diseases
Epidermis
Monocytes
Nitric Oxide
T-Lymphocytes
Messenger RNA
Skin
Infection

Keywords

  • Autoimmune disease
  • CD11c
  • Tip-DC

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Increase in TNF-α and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a). / Lowes, Michelle A.; Chamian, Francesca; Abello, Maria Veronica; Fuentes-Duculan, Judilyn; Lin, Shao Lee; Nussbaum, Rachel; Novitskaya, Inna; Carbonaro, Henrietta; Cardinale, Irma; Kikuchi, Toyoko; Gilleaudeau, Patricia; Sullivan-Whalen, Mary; Wittkowski, Knut M.; Papp, Kim; Garovoy, Marvin; Dummer, Wolfgang; Steinman, Ralph M.; Krueger, James G.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 52, 27.12.2005, p. 19057-19062.

Research output: Contribution to journalArticle

Lowes, MA, Chamian, F, Abello, MV, Fuentes-Duculan, J, Lin, SL, Nussbaum, R, Novitskaya, I, Carbonaro, H, Cardinale, I, Kikuchi, T, Gilleaudeau, P, Sullivan-Whalen, M, Wittkowski, KM, Papp, K, Garovoy, M, Dummer, W, Steinman, RM & Krueger, JG 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, vol. 102, no. 52, pp. 19057-19062. https://doi.org/10.1073/pnas.0509736102
Lowes, Michelle A. ; Chamian, Francesca ; Abello, Maria Veronica ; Fuentes-Duculan, Judilyn ; Lin, Shao Lee ; Nussbaum, Rachel ; Novitskaya, Inna ; Carbonaro, Henrietta ; Cardinale, Irma ; Kikuchi, Toyoko ; Gilleaudeau, Patricia ; Sullivan-Whalen, Mary ; Wittkowski, Knut M. ; Papp, Kim ; Garovoy, Marvin ; Dummer, Wolfgang ; Steinman, Ralph M. ; Krueger, James G. / Increase in TNF-α and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a). In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 52. pp. 19057-19062.
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AU - Lin, Shao Lee

AU - Nussbaum, Rachel

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AU - Gilleaudeau, Patricia

AU - Sullivan-Whalen, Mary

AU - Wittkowski, Knut M.

AU - Papp, Kim

AU - Garovoy, Marvin

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AU - Steinman, Ralph M.

AU - Krueger, James G.

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