title: Human myeloid dendritic cells are refractory to tryptophan metabolites.
abstract: The enzyme indoleamine 2,3-dioxygenase (IDO) degrades the essential amino acid tryptophan and is expressed, among other cell types, in immune cells such as dendritic cells (DCs), monocytes, and macrophages. It has been shown that the activity of IDO has a broad regulatory function in the immune system by inhibiting effector T-cell responses, inducing regulatory T cells and facilitating the development of regulatory DCs. The degradation of tryptophan has 2 consequences, both of which have been postulated to be physiologically relevant, namely the reduction of tryptophan levels and the accumulation of tryptophan catabolites. Recently, we have shown that DCs that had differentiated under low-tryptophan conditions acquire a tolerogenic phenotype with increased expression of the inhibitory receptors immunoglobulin-like transcript 2 (ILT2), ILT3, and ILT4. In the present study, we investigated the effect of distinct tryptophan catabolites on the function of human DCs and the expression of ILT2, ILT3, and ILT4 on these cells. We show that, in contrast to low tryptophan levels alone, the combination of several metabolites along the tryptophan-kynurenine degradation pathway during DC differentiation does not induce ILT2, ILT3, or ILT4 on these DCs and does not reduce the T-cell stimulatory capacity of these DCs.
authors.affiliation: Department of Dermatology and Allergology, Friedrich-Wilhelms-University, Bonn, Germany. d.bubnoff@uni-bonn.de
authors.forename: Dagmar
authors.initials: D
authors.lastname: von Bubnoff
authors.forename: Helene
authors.initials: H
authors.lastname: Wilms
authors.forename: Marina
authors.initials: M
authors.lastname: Scheler
authors.forename: Manuela
authors.initials: M
authors.lastname: Brenk
authors.forename: Susanne
authors.initials: S
authors.lastname: Koch
authors.forename: Thomas
authors.initials: T
authors.lastname: Bieber
mesh_terms: D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007111:Immunity, Cellular; D007150:Immunohistochemistry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology / Q000378:metabolism*; D007737:Kynurenine / Q000378:metabolism / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000201:enzymology* / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009000:Monocytes / Q000201:enzymology* / Q000276:immunology; D017378:Quinolinic Acid / Q000378:metabolism / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000096:biosynthesis; D050378:T-Lymphocytes, Regulatory / Q000201:enzymology* / Q000276:immunology; D014364:Tryptophan / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000906:Antibodies; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; C491341:LILRB2 protein, human; C107907:LILRB4 protein, human; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D007737:Kynurenine; D014364:Tryptophan; D017378:Quinolinic Acid