Εμφάνιση απλής εγγραφής

dc.creatorEleftheriadis, T.en
dc.creatorPissas, G.en
dc.creatorAntoniadi, G.en
dc.creatorLiakopoulos, V.en
dc.creatorStefanidis, I.en
dc.date.accessioned2015-11-23T10:26:12Z
dc.date.available2015-11-23T10:26:12Z
dc.date.issued2015
dc.identifier10.1111/imm.12502
dc.identifier.issn192805
dc.identifier.urihttp://hdl.handle.net/11615/27331
dc.description.abstractIndoleamine 2,3-dioxygenase (IDO) is expressed in antigen-presenting cells and exerts immunosuppressive effects on CD4+ T cells. One mechanism is through the inhibition of aerobic glycolysis. Another prerequisite for T-cell proliferation and differentiation into effector cells is increased fatty acid (FA) synthesis. The effect of IDO on enzymes involved in FA synthesis was evaluated in primary human cells both in mixed lymphocyte reactions in the presence or not of the IDO inhibitor 1-dl-methyl-tryptophan, and in stimulated CD4+ T cells in the presence or not of the general control non-derepressible 2 (GCN2) kinase activator tryptophanol (TRP). IDO or TRP inhibited cell proliferation. By assessing the level of GCN2 kinase or mammalian target of rapamycin complex 1 substrates along with a kynurenine free system we showed that IDO exerts its effect mainly through activation of GCN2 kinase. IDO or TRP down-regulated ATP-citrate lyase and acetyl coenzyme A carboxylase 1, key enzymes involved in FA synthesis. Also, IDO or TRP altered the expression of enzymes that control the availability of carbon atoms for FA synthesis, such as lactate dehydrogenase-A, pyruvate dehydrogenase, glutaminase 1 and glutaminase 2, in a way that inhibits FA synthesis. In conclusion, IDO through GCN2 kinase activation inhibits CD4+ T-cell proliferation and down-regulates key enzymes that directly or indirectly promote FA synthesis, a prerequisite for CD4+ T-cell proliferation and differentiation into effector cell lineages. © 2015 John Wiley & Sons Ltd.en
dc.source.urihttp://www.scopus.com/inward/record.url?eid=2-s2.0-84941742185&partnerID=40&md5=0f85a6cc81118f25a9a76b2e8094a227
dc.subjectAcetyl coenzyme A carboxylase 1en
dc.subjectATP-citrate lyaseen
dc.subjectFatty aciden
dc.subjectGeneral control non-derepressible 2 kinaseen
dc.subjectIndoleamine 2,3-dioxygenaseen
dc.subjectT cellsen
dc.subjectacetyl coenzyme A carboxylaseen
dc.subjectadenosine triphosphate citrate synthaseen
dc.subjectgeneral control non derepressible 2 kinaseen
dc.subjectglutaminaseen
dc.subjectglutaminase 2en
dc.subjectindoleamine 2,3 dioxygenaseen
dc.subjectinitiation factor 2alphaen
dc.subjectlactate dehydrogenaseen
dc.subjectlactate dehydrogenase Aen
dc.subjectmammalian target of rapamycin complex 1en
dc.subjectn methyltryptophanen
dc.subjectphosphotransferaseen
dc.subjectpyruvate dehydrogenaseen
dc.subjecttryptophanen
dc.subjectunclassified drugen
dc.subjectadulten
dc.subjectalloimmunityen
dc.subjectArticleen
dc.subjectCD4+ T lymphocyteen
dc.subjectcell expansionen
dc.subjectcell viabilityen
dc.subjectdown regulationen
dc.subjectenzyme activationen
dc.subjectfatty acid synthesisen
dc.subjectfemaleen
dc.subjecthumanen
dc.subjecthuman cellen
dc.subjectlymphocyte differentiationen
dc.subjectlymphocyte proliferationen
dc.subjectmaleen
dc.subjectmixed lymphocyte reactionen
dc.subjectperipheral blood mononuclear cellen
dc.subjectpriority journalen
dc.subjectprotein degradationen
dc.subjectprotein expressionen
dc.subjectprotein phosphorylationen
dc.subjectT lymphocyte activationen
dc.subjectupregulationen
dc.titleIndoleamine 2,3-dioxygenase depletes tryptophan, activates general control non-derepressible 2 kinase and down-regulates key enzymes involved in fatty acid synthesis in primary human CD4+ T cellsen
dc.typejournalArticleen


Αρχεία σε αυτό το τεκμήριο

ΑρχείαΜέγεθοςΤύποςΠροβολή

Δεν υπάρχουν αρχεία που να σχετίζονται με αυτό το τεκμήριο.

Αυτό το τεκμήριο εμφανίζεται στις ακόλουθες συλλογές

Εμφάνιση απλής εγγραφής