Document Detail


Indoleamine 2,3-dioxygenase (IDO): the antagonist of type I interferon-driven skin inflammation?
MedLine Citation:
PMID:  18055547     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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-alpha/beta 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-alpha 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.
Authors:
Marina Scheler; Joerg Wenzel; Thomas Tüting; Osamu Takikawa; Thomas Bieber; Dagmar von Bubnoff
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-11-30
Journal Detail:
Title:  The American journal of pathology     Volume:  171     ISSN:  0002-9440     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-12-10     Completed Date:  2008-02-08     Revised Date:  2013-03-21    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1936-43     Citation Subset:  AIM; IM    
Affiliation:
Department of Dermatology, Friedrich-Wilhelms University, Sigmund Freud-Strasse 25, 53105 Bonn, Germany. marina.scheler@ukb.uni-bonn.de
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD / analysis
Antigens, CD11c / analysis
Antigens, Differentiation, Myelomonocytic / analysis
Dendritic Cells / enzymology,  immunology
Dermatitis / enzymology,  immunology*,  pathology
Female
Humans
Indoleamine-Pyrrole 2,3,-Dioxygenase / analysis,  metabolism*
Interferon Type I / antagonists & inhibitors*,  metabolism
Interferon-alpha / antagonists & inhibitors,  metabolism
Interferon-gamma / metabolism
Lichen Planus / enzymology,  immunology*,  pathology
Male
Myeloid Cells / enzymology,  immunology
Psoriasis / enzymology,  immunology,  pathology
S100 Proteins / analysis
T-Lymphocytes / immunology
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Antigens, CD11c; 0/Antigens, Differentiation, Myelomonocytic; 0/CD68 antigen, human; 0/Indoleamine-Pyrrole 2,3,-Dioxygenase; 0/Interferon Type I; 0/Interferon-alpha; 0/S100 Proteins; 82115-62-6/Interferon-gamma
Comments/Corrections

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