Indoleamine 2,3-dioxygenase (IDO): the antagonist of type I interferon-driven skin inflammation?
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.
Department of Dermatology, Friedrich-Wilhelms University, Sigmund Freud-Strasse 25, 53105 Bonn, Germany. marina.scheler@ukb.uni-bonn.de
Marina
M
Scheler
Joerg
J
Wenzel
Thomas
T
Tüting
Osamu
O
Takikawa
Thomas
T
Bieber
Dagmar
D
von Bubnoff
D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D039521:CD11c Antigen / Q000032:analysis; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology; D003872:Dermatitis / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000032:analysis / Q000378:metabolism*; D007370:Interferon Type I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016898:Interferon-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D008010:Lichen Planus / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D008297:Male; D022423:Myeloid Cells / Q000201:enzymology / Q000276:immunology; D011565:Psoriasis / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D009418:S100 Proteins / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D039521:CD11c Antigen; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007370:Interferon Type I; D016898:Interferon-alpha; D007371:Interferon-gamma; D009418:S100 Proteins; C067980:CD68 antigen, human; D000097382:CD68 Molecule