Open Access

Gain‑of‑function of IDO in DCs inhibits T cell immunity by metabolically regulating surface molecules and cytokines

  • Authors:
    • Fengge Wang
    • Lei Liu
    • Juncheng Wang
    • Meng Liu
    • Wenjie Zhang
    • Lin Zhao
    • Chengfeng Zhai
    • Yuekang Xu
  • View Affiliations

  • Published online on: April 3, 2023     https://doi.org/10.3892/etm.2023.11933
  • Article Number: 234
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Both tolerogenicity and immunogenicity of dendritic cells (DCs) are regulated by their intracellular metabolism. As a rate‑limiting enzyme of tryptophan (Trp) metabolism, indoleamine 2,3‑dioxygenase (IDO) is involved in regulating the functions of numerous cell types, including DCs, a subset of which has a high capacity for producing IDO to control over‑activated inflammation. To identify the mechanisms of IDO in DCs, stable DC lines with both gain‑ and reduction‑of‑function of IDO were established using a recombinant DNA technique. Although the IDO variation did not affect DC survival and migration, it altered Trp metabolism and other features of DCs analyzed by high‑performance liquid chromatography and flow cytometry. On the surface of the DCs, IDO inhibited co‑stimulatory CD86 but promoted co‑inhibitory programmed cell death ligand 1 expression, and suppressed the antigen uptake, which ultimately led to the compromised ability of DCs to activate T cells. Furthermore, IDO also suppressed IL‑12 secretion but enhanced that of IL‑10 in DCs, which eventually induced T cells into tolerogenic phenotypes by inhibiting the differentiation of Th1 but promoting that of regulatory T cells. Collectively, the findings of the present study demonstrated that IDO is a key molecule for tolerogenic DC induction by metabolically regulating surface molecule and cytokine expression. This conclusion may lead to the targeted development of therapeutic drugs for autoimmune diseases.
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May-2023
Volume 25 Issue 5

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Wang F, Liu L, Wang J, Liu M, Zhang W, Zhao L, Zhai C and Xu Y: Gain‑of‑function of IDO in DCs inhibits T cell immunity by metabolically regulating surface molecules and cytokines. Exp Ther Med 25: 234, 2023.
APA
Wang, F., Liu, L., Wang, J., Liu, M., Zhang, W., Zhao, L. ... Xu, Y. (2023). Gain‑of‑function of IDO in DCs inhibits T cell immunity by metabolically regulating surface molecules and cytokines. Experimental and Therapeutic Medicine, 25, 234. https://doi.org/10.3892/etm.2023.11933
MLA
Wang, F., Liu, L., Wang, J., Liu, M., Zhang, W., Zhao, L., Zhai, C., Xu, Y."Gain‑of‑function of IDO in DCs inhibits T cell immunity by metabolically regulating surface molecules and cytokines". Experimental and Therapeutic Medicine 25.5 (2023): 234.
Chicago
Wang, F., Liu, L., Wang, J., Liu, M., Zhang, W., Zhao, L., Zhai, C., Xu, Y."Gain‑of‑function of IDO in DCs inhibits T cell immunity by metabolically regulating surface molecules and cytokines". Experimental and Therapeutic Medicine 25, no. 5 (2023): 234. https://doi.org/10.3892/etm.2023.11933