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  •   University of Thessaly Institutional Repository
  • Επιστημονικές Δημοσιεύσεις Μελών ΠΘ (ΕΔΠΘ)
  • Δημοσιεύσεις σε περιοδικά, συνέδρια, κεφάλαια βιβλίων κλπ.
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  •   University of Thessaly Institutional Repository
  • Επιστημονικές Δημοσιεύσεις Μελών ΠΘ (ΕΔΠΘ)
  • Δημοσιεύσεις σε περιοδικά, συνέδρια, κεφάλαια βιβλίων κλπ.
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Indoleamine 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 cells

Thumbnail
Author
Eleftheriadis, T.; Pissas, G.; Antoniadi, G.; Liakopoulos, V.; Stefanidis, I.
Date
2015
DOI
10.1111/imm.12502
Keyword
Acetyl coenzyme A carboxylase 1
ATP-citrate lyase
Fatty acid
General control non-derepressible 2 kinase
Indoleamine 2,3-dioxygenase
T cells
acetyl coenzyme A carboxylase
adenosine triphosphate citrate synthase
general control non derepressible 2 kinase
glutaminase
glutaminase 2
indoleamine 2,3 dioxygenase
initiation factor 2alpha
lactate dehydrogenase
lactate dehydrogenase A
mammalian target of rapamycin complex 1
n methyltryptophan
phosphotransferase
pyruvate dehydrogenase
tryptophan
unclassified drug
adult
alloimmunity
Article
CD4+ T lymphocyte
cell expansion
cell viability
down regulation
enzyme activation
fatty acid synthesis
female
human
human cell
lymphocyte differentiation
lymphocyte proliferation
male
mixed lymphocyte reaction
peripheral blood mononuclear cell
priority journal
protein degradation
protein expression
protein phosphorylation
T lymphocyte activation
upregulation
Metadata display
Abstract
Indoleamine 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.
URI
http://hdl.handle.net/11615/27331
Collections
  • Δημοσιεύσεις σε περιοδικά, συνέδρια, κεφάλαια βιβλίων κλπ. [19674]

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Η δικτυακή πύλη της Ευρωπαϊκής Ένωσης
Ψηφιακή Ελλάδα
ΕΣΠΑ 2007-2013
Με τη συγχρηματοδότηση της Ελλάδας και της Ευρωπαϊκής Ένωσης
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Η δικτυακή πύλη της Ευρωπαϊκής Ένωσης
Ψηφιακή Ελλάδα
ΕΣΠΑ 2007-2013
Με τη συγχρηματοδότηση της Ελλάδας και της Ευρωπαϊκής Ένωσης
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