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

347 Scopus citations

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

Keywords

  • Autoimmune disease
  • CD11c
  • Tip-DC

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Increase in TNF-α and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a)'. Together they form a unique fingerprint.

  • Cite this

    Lowes, M. A., Chamian, F., Abello, M. V., Fuentes-Duculan, J., Lin, S. L., Nussbaum, R., Novitskaya, I., Carbonaro, H., Cardinale, I., Kikuchi, T., Gilleaudeau, P., Sullivan-Whalen, M., Wittkowski, K. M., Papp, K., Garovoy, M., Dummer, W., Steinman, R. M., & Krueger, J. G. (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. https://doi.org/10.1073/pnas.0509736102