Indoleamine 2,3-dioxygenase, by degrading L-tryptophan, enhances carnitine palmitoyltransferase I activity and fatty acid oxidation, and exerts fatty acid-dependent effects in human alloreactive CD4+ T-cells

  • Authors:
    • Theodoros Eleftheriadis
    • Georgios Pissas
    • Maria Sounidaki
    • Konstantina Tsogka
    • Nikolaos Antoniadis
    • Georgia Antoniadi
    • Vassilios Liakopoulos
    • Ioannis Stefanidis
  • View Affiliations

  • Published online on: September 23, 2016     https://doi.org/10.3892/ijmm.2016.2750
  • Pages: 1605-1613
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Indoleamine 2,3-dioxygenase (IDO) is expressed in antigen-presenting cells and by degrading L-tryptophan along the kynurenine pathway suppresses CD4+ T-cell proliferation, induces apoptosis and promotes differentiation towards a regulatory as opposed to an effector phenotype. Recent findings revealed that the above effects may be mediated through alterations in T-cell metabolism. In this study, the effect of IDO on fatty acid β-oxidation in CD4+ T-cells was evaluated in human mixed lymphocyte reactions (MLRs) using the IDO inhibitor, 1-DL-methyl-tryptophan. Protein analysis of CD4+ T-cells isolated from the MLR showed that L-tryptophan degradation acts by activating the general control non‑derepressible 2 kinase and aryl-hydrocarbon receptor in T-cells. In the absence of IDO inhibition, fatty acid oxidation increased along with increased activity of carnitine palmitoyltransferase I (CPT1), the latter due to the increased expression of CPT1 isoenzymes and alterations in acetyl-CoA carboxylase 2, the enzyme that controls CPT1 activity. Increased fatty acid oxidation due to the action of IDO was accompanied by an increased expression of forkhead box P3 (FoxP3) and a decreased expression of related orphan receptor γt (RORγt), the signature transcription factors of regulatory T-cells and T helper 17 cells, respectively. However, in MLR and in the presence of fatty acid in the culture medium, IDO did not inhibit proliferation. Additionally, fatty acid protected the CD4+ T-cells against apoptosis. Thus, IDO, by degrading L-tryptophan, enhances CPT1 activity and fatty acid oxidation, and exerts fatty acid-dependent effects in human alloreactive CD4+ T-cells.
View Figures
View References

Related Articles

Journal Cover

November-2016
Volume 38 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Eleftheriadis T, Pissas G, Sounidaki M, Tsogka K, Antoniadis N, Antoniadi G, Liakopoulos V and Stefanidis I: Indoleamine 2,3-dioxygenase, by degrading L-tryptophan, enhances carnitine palmitoyltransferase I activity and fatty acid oxidation, and exerts fatty acid-dependent effects in human alloreactive CD4+ T-cells. Int J Mol Med 38: 1605-1613, 2016
APA
Eleftheriadis, T., Pissas, G., Sounidaki, M., Tsogka, K., Antoniadis, N., Antoniadi, G. ... Stefanidis, I. (2016). Indoleamine 2,3-dioxygenase, by degrading L-tryptophan, enhances carnitine palmitoyltransferase I activity and fatty acid oxidation, and exerts fatty acid-dependent effects in human alloreactive CD4+ T-cells. International Journal of Molecular Medicine, 38, 1605-1613. https://doi.org/10.3892/ijmm.2016.2750
MLA
Eleftheriadis, T., Pissas, G., Sounidaki, M., Tsogka, K., Antoniadis, N., Antoniadi, G., Liakopoulos, V., Stefanidis, I."Indoleamine 2,3-dioxygenase, by degrading L-tryptophan, enhances carnitine palmitoyltransferase I activity and fatty acid oxidation, and exerts fatty acid-dependent effects in human alloreactive CD4+ T-cells". International Journal of Molecular Medicine 38.5 (2016): 1605-1613.
Chicago
Eleftheriadis, T., Pissas, G., Sounidaki, M., Tsogka, K., Antoniadis, N., Antoniadi, G., Liakopoulos, V., Stefanidis, I."Indoleamine 2,3-dioxygenase, by degrading L-tryptophan, enhances carnitine palmitoyltransferase I activity and fatty acid oxidation, and exerts fatty acid-dependent effects in human alloreactive CD4+ T-cells". International Journal of Molecular Medicine 38, no. 5 (2016): 1605-1613. https://doi.org/10.3892/ijmm.2016.2750