Published online before print November 30, 2007

This Article Full Text (Rapid PDF) All Versions of this Article: ajpath.2007.070281v1 171/6/1936    most recent Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Scheler, M. Articles by von Bubnoff, D. Search for Related Content PubMed PubMed Citation Articles by Scheler, M. Articles by von Bubnoff, D.

Copyright © 2007 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2007.070281

Accepted for publication September 5, 2007.

Article

Indoleamine 2,3-Dioxygenase (IDO). The Antagonist of Type I Interferon-Driven Skin Inflammation?

Marina Scheler^*@, Joerg Wenzel^*, Thomas Tüting^*, Osamu Takikawa, Thomas Bieber^*, and Dagmar von Bubnoff^*

From the Department of Dermatology,* Friedrich-Wilhelms-University, Bonn, Germany; and the National Institute for Longevity Science, National Center for Geriatrics and Gerontology, Aichi, Japan

^@ To whom correspondence should be addressed. E-mail: marina.scheler{at}ukb.uni-bonn.de.

	Abstract

Recent studies have provided evidence that a type I interferon (IFN)-driven immune response might play an important role in the pathogenesis of lichen planus (LP), an inflammatory disorder of the skin of unclear etiology. Plasmacytoid dendritic cells in affected skin from LP have been proposed to produce IFN-/ locally, which leads to the expression of IFN-inducible chemokines such as IP10/CXCL10 in the epidermis. This chemokine recruits chemokine receptor CXCR3-expressing T-lymphocytes into the skin via CXCR3/IP10 interactions. Indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan and suppresses T-cell proliferation, is induced by IFNs and other inflammatory cytokines. We show that type I IFN-mediated skin disorders, such as LP, strongly express IDO in lesional skin. This expression closely correlates to the expression of the highly specific type I IFN marker MxA. We further demonstrate that the IDO⁺ cells in LP are large myeloid CD11c⁺S100⁺CD68^- dendritic cells. Accordingly, CD11c⁺ antigen-presenting cells significantly up-regulate IDO gene expression and intracellular IDO protein expression after stimulation with IFN- in vitro. These findings reveal that both proinflammatory and counterregulatory mechanisms are operative in cutaneous lesions of LP. We propose that the balance of these mechanisms may be involved in the pathogenesis of this disorder.