title: Different partners, opposite outcomes: a new perspective of the immunobiology of indoleamine 2,3-dioxygenase.
abstract: Indoleamine 2,3-dioxygenase (IDO), a metabolic enzyme that catalyzes tryptophan conversion into kynurenines, is a crucial regulator of immunity. Altered IDO activity is often associated with pathology, including neoplasia and autoimmunity. IDO is highly expressed in dendritic cells (DCs) that exploit the enzyme's activity and the production of tryptophan catabolites to regulate immune responses by acting on several cell types, including T lymphocytes, of which they promote a regulatory phenotype. IDO also contains immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that, once bound by distinct molecular partners, will either promote degradation or initiate signaling activity and self-maintenance of the enzyme. We here discuss how ITIM-dependent molecular events can affect the functional plasticity of IDO by modifying the protein half-life and its enzymic and nonenzymic functions.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy. ciry72@hotmail.com
authors.forename: Ciriana
authors.initials: C
authors.lastname: Orabona
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Pallotta
authors.forename: Ursula
authors.initials: U
authors.lastname: Grohmann
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D003713:Dendritic Cells / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism*; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics / Q000378:metabolism; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism; D011971:Receptors, Immunologic / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D015850:Interleukin-6; D016328:NF-kappa B; D011971:Receptors, Immunologic; D016212:Transforming Growth Factor beta; D051076:Proto-Oncogene Proteins c-fyn; D053592:Interleukin-1 Receptor-Associated Kinases; D051550:I-kappa B Kinase; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6