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http://purl.uniprot.org/citations/26497245http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/26497245http://www.w3.org/2000/01/rdf-schema#comment"Tryptophan metabolites, including kynurenine, 3-hydroxyanthranilic acid, and picolinic acid, are key mediators of immunosuppression by cells expressing the tryptophan-catabolizing enzyme indoleamine2,3-dioxygenase. In this study, we assessed the influence of picolinic acid on cell viability and effector functions of CD4(+)T cells following in vitro activation with agonistic anti-CD3/anti-CD28 antibodies. In contrast to kynurenine and 3-hydroxyanthranilic acid, exposure of T cells with picolinic acid did not affect cell viability, whereas proliferation and metabolic activity were suppressed in a dose-dependent manner. On the other hand, cytokine secretion and up-regulation of cell surface activation markers were not or only weakly inhibited by picolinic acid. Picolinic acid exposure induced a state of deep anergy that could not be overcome by the addition of exogenous IL-2 and inhibited Th cell polarization. On the molecular level, important upstream signaling molecules, such as the MAPKs ERK and p38 and the mammalian target of rapamycin target protein S6 ribosomal protein, were not affected by picolinic acid. Likewise, NFAT, NF-κB, and AP-1 promoter activity in Jurkat T cells was not influenced by exposure to picolinic acid. Whereas transcriptional levels of v-myc avian myelocytomatosis viral oncogene homolog were not affected by picolinic acid, phosphorylation at Ser62 was strongly reduced in picolinic acid-exposed T cells following activation. In conclusion, picolinic acid mediates a unique immunosuppressive program in T cells, mainly inhibiting cell cycle and metabolic activity, while leaving other effector functions intact. These functional features are accompanied by reduced phosphorylation of v-myc avian myelocytomatosis viral oncogene homolog. It remains to be determined whether this effect is mediated by direct inhibition of ERK activity or whether indirect mechanisms apply."xsd:string
http://purl.uniprot.org/citations/26497245http://purl.org/dc/terms/identifier"doi:10.1189/jlb.3a0315-135r"xsd:string
http://purl.uniprot.org/citations/26497245http://purl.uniprot.org/core/author"Steinberger P."xsd:string
http://purl.uniprot.org/citations/26497245http://purl.uniprot.org/core/author"Pickl W.F."xsd:string
http://purl.uniprot.org/citations/26497245http://purl.uniprot.org/core/author"Jutz S."xsd:string
http://purl.uniprot.org/citations/26497245http://purl.uniprot.org/core/author"Hoermann G."xsd:string
http://purl.uniprot.org/citations/26497245http://purl.uniprot.org/core/author"Marculescu R."xsd:string
http://purl.uniprot.org/citations/26497245http://purl.uniprot.org/core/author"Schmidt R.L."xsd:string
http://purl.uniprot.org/citations/26497245http://purl.uniprot.org/core/author"Greiner G."xsd:string
http://purl.uniprot.org/citations/26497245http://purl.uniprot.org/core/author"Ratzinger F."xsd:string
http://purl.uniprot.org/citations/26497245http://purl.uniprot.org/core/author"Schmetterer K.G."xsd:string
http://purl.uniprot.org/citations/26497245http://purl.uniprot.org/core/author"Loacker L.J."xsd:string
http://purl.uniprot.org/citations/26497245http://purl.uniprot.org/core/author"Prodinger J."xsd:string
http://purl.uniprot.org/citations/26497245http://purl.uniprot.org/core/author"Witzeneder N."xsd:string
http://purl.uniprot.org/citations/26497245http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/26497245http://purl.uniprot.org/core/name"J Leukoc Biol"xsd:string
http://purl.uniprot.org/citations/26497245http://purl.uniprot.org/core/pages"583-594"xsd:string
http://purl.uniprot.org/citations/26497245http://purl.uniprot.org/core/title"The tryptophan metabolite picolinic acid suppresses proliferation and metabolic activity of CD4+ T cells and inhibits c-Myc activation."xsd:string
http://purl.uniprot.org/citations/26497245http://purl.uniprot.org/core/volume"99"xsd:string
http://purl.uniprot.org/citations/26497245http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/26497245
http://purl.uniprot.org/citations/26497245http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/26497245
http://purl.uniprot.org/uniprot/#_A0A0B4J1R1-mappedCitation-26497245http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26497245
http://purl.uniprot.org/uniprot/#_A0N2G3-mappedCitation-26497245http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26497245
http://purl.uniprot.org/uniprot/#_A0A224B085-mappedCitation-26497245http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26497245