{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:13:16Z","timestamp":1790507596604,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,7,27]],"date-time":"2015-07-27T00:00:00Z","timestamp":1437955200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Indoleamine 2,3\u2010dioxygenase (<jats:styled-content style=\"fixed-case\">IDO<\/jats:styled-content>) is expressed in antigen\u2010presenting cells and exerts immunosuppressive effects on <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> T cells. One mechanism is through the inhibition of aerobic glycolysis. Another prerequisite for T\u2010cell proliferation and differentiation into effector cells is increased fatty acid (<jats:styled-content style=\"fixed-case\">FA<\/jats:styled-content>) synthesis. The effect of <jats:styled-content style=\"fixed-case\">IDO<\/jats:styled-content> on enzymes involved in <jats:styled-content style=\"fixed-case\">FA<\/jats:styled-content> synthesis was evaluated in primary human cells both in mixed lymphocyte reactions in the presence or not of the <jats:styled-content style=\"fixed-case\">IDO<\/jats:styled-content> inhibitor 1\u2010<jats:sc>dl<\/jats:sc>\u2010methyl\u2010tryptophan, and in stimulated <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> T cells in the presence or not of the general control non\u2010derepressible 2 (<jats:styled-content style=\"fixed-case\">GCN<\/jats:styled-content>2) kinase activator tryptophanol (<jats:styled-content style=\"fixed-case\">TRP<\/jats:styled-content>). <jats:styled-content style=\"fixed-case\">IDO<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">TRP<\/jats:styled-content> inhibited cell proliferation. By assessing the level of <jats:styled-content style=\"fixed-case\">GCN<\/jats:styled-content>2 kinase or mammalian target of rapamycin complex 1 substrates along with a kynurenine free system we showed that <jats:styled-content style=\"fixed-case\">IDO<\/jats:styled-content> exerts its effect mainly through activation of <jats:styled-content style=\"fixed-case\">GCN<\/jats:styled-content>2 kinase. <jats:styled-content style=\"fixed-case\">IDO<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">TRP<\/jats:styled-content> down\u2010regulated <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>\u2010citrate lyase and acetyl coenzyme A carboxylase 1, key enzymes involved in <jats:styled-content style=\"fixed-case\">FA<\/jats:styled-content> synthesis. Also, <jats:styled-content style=\"fixed-case\">IDO<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">TRP<\/jats:styled-content> altered the expression of enzymes that control the availability of carbon atoms for <jats:styled-content style=\"fixed-case\">FA<\/jats:styled-content> synthesis, such as lactate dehydrogenase\u2010A, pyruvate dehydrogenase, glutaminase 1 and glutaminase 2, in a way that inhibits <jats:styled-content style=\"fixed-case\">FA<\/jats:styled-content> synthesis. In conclusion, <jats:styled-content style=\"fixed-case\">IDO<\/jats:styled-content> through <jats:styled-content style=\"fixed-case\">GCN<\/jats:styled-content>2 kinase activation inhibits <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> T\u2010cell proliferation and down\u2010regulates key enzymes that directly or indirectly promote <jats:styled-content style=\"fixed-case\">FA<\/jats:styled-content> synthesis, a prerequisite for <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> T\u2010cell proliferation and differentiation into effector cell lineages.<\/jats:p>","DOI":"10.1111\/imm.12502","type":"journal-article","created":{"date-parts":[[2015,7,4]],"date-time":"2015-07-04T13:22:48Z","timestamp":1436016168000},"page":"292-300","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Indoleamine 2,3\u2010dioxygenase depletes tryptophan, activates general control non\u2010derepressible 2 kinase and down\u2010regulates key enzymes involved in fatty acid synthesis in primary human <scp>CD<\/scp>4<sup>+<\/sup> T cells"],"prefix":"10.1111","volume":"146","author":[{"given":"Theodoros","family":"Eleftheriadis","sequence":"first","affiliation":[{"name":"Department of Nephrology Medical School University of Thessaly Larissa Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Pissas","sequence":"additional","affiliation":[{"name":"Department of Nephrology Medical School University of Thessaly Larissa Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Antoniadi","sequence":"additional","affiliation":[{"name":"Department of Nephrology Medical School University of Thessaly Larissa Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassilios","family":"Liakopoulos","sequence":"additional","affiliation":[{"name":"Department of 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