Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses

Lisa C. Zaba, Irma Cardinale, Patricia Gilleaudeau, Mary Sullivan-Whalen, Mayte Suárez Fariñas, Judilyn Fuentes-Duculan, Inna Novitskaya, Artemis Khatcherian, Mark J. Bluth, Michelle A. Lowes, James G. Krueger

Research output: Contribution to journalArticle

482 Scopus citations

Abstract

Biological agents have dramatically improved treatment options for patients with severe psoriasis. Etanercept (tumor necrosis factor [TNF] receptor-immunoglobulin fusion protein) is an effective treatment for many psoriasis patients, and blockade of TNF is considered to be its primary action. However, in this clinical trial, we show that etanercept has early inhibitory effects on a newly appreciated type of T cells: T helper type 17 (Th17) cells. Etanercept reduced the inflammatory dendritic cell products that drive Th17 cell proliferation (interleukin [IL] 23), as well as Th17 cell products and downstream effector molecules (IL-17, IL-22, CC chemokine ligand 20, and β-defensin 4). In contrast, Th1 cellular products and effector molecules (interferon γ, lymphotoxin α, and myxovirus resistance 1) were reduced late in disease resolution. This study suggests a role for Th17 in addition to Th1 cells in the pathogenesis of psoriasis. Th17 cells may be particularly important in driving epidermal activation in psoriatic plaques, whereas Th1 cells must also be eliminated for final disease resolution. JEM

Original languageEnglish (US)
Pages (from-to)3183-3194
Number of pages12
JournalJournal of Experimental Medicine
Volume204
Issue number13
DOIs
StatePublished - Dec 24 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Zaba, L. C., Cardinale, I., Gilleaudeau, P., Sullivan-Whalen, M., Fariñas, M. S., Fuentes-Duculan, J., Novitskaya, I., Khatcherian, A., Bluth, M. J., Lowes, M. A., & Krueger, J. G. (2007). Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses. Journal of Experimental Medicine, 204(13), 3183-3194. https://doi.org/10.1084/jem.20071094