CpG олигонуклеотиды с модифицированными фосфатными группами индуцируют созревание миелоидных дендритных клеток человека in vitro

Translated title of the contribution: Phosphate-modif ied CpG oligonucleotides induce in vitro maturation of human myeloid dendritic cells

A. A. Ostanin, O. Y. Leplina, E. A. Burakova, T. V. Tyrinova, A. A. Fokina, A. S. Proskurina, S. S. Bogachev, D. A. Stetsenko, E. R. Chernykh

Research output: Contribution to journalArticlepeer-review

Abstract

Myeloid dendritic cells (DCs) play an important role in the immune response; therefore, the search for compounds that can effectively activate DCs is a needful goal. This study was aimed to investigate the effect of synthetic CpG oligodeoxynucleotides (CpG-ODN) on the maturation and allostimulatory activity of myeloid DCs in comparison with other PAMP and DAMP molecules. For the research, we synthesized known CpG-ODN class C (SD-101 and D-SL03) containing thiophosphate internucleotide groups, and their original phosphate-modified analogues (SD-101M and D-SL03M) with mesylphosphoramide internucleotide groups (M = μ-modification). The effects of CpG-ODN and other activators were evaluated on DCs generated from blood monocytes in the presence of GM-CSF and IFN-α (IFN-DC) or IL-4 (IL4-DC). Evaluation of the intracellular TLR-9 expression showed that both types of DCs (IFN-DC and IL4-DC) contained on average 52 and 80 % of TLR-9-positive cells, respectively. The CpG-ODNs studied enhanced the allostimulatory activity of IFN-DCs, and the effect of μ-modified CpG-ODNs was higher than that of CpG-ODNs with thiophosphate groups. The stimulating effect of CpG-ODN at a dose of 1.0 μg/ml was comparable (for D-SL03, D-SL03M, SD-101) with or exceeded (for SD-101M) the effect of LPS at a dose of 10 μg/ml. At the same time, IFN-DCs were characterized by greater sensitivity to the action of CpG-ODNs than IL4-DCs. The enhancement of DC allostimulatory activity in the presence of CpG-ODNs was associated with the induction of final DC maturation, which was confirmed by a significant decrease in the number of CD14+DC, an increase in mature CD83+DC and a trend towards an increase in CD86+DC. Interestingly, the characteristic ability of LPS to enhance the expression of the co-stimulatory molecule OX40L on DCs was revealed only for the μ-analogue SD-101M. In addition, CpG-ODNs (SD-101 and SD-101M) had a stimulatory effect on IFN-γ production comparable to the action of LPS. The data obtained indicate a stimulating effect of CpG-ODN on the maturation and allostimulatory activity of human myeloid DCs, which is more pronounced for μ-modified analogs.

Translated title of the contributionPhosphate-modif ied CpG oligonucleotides induce in vitro maturation of human myeloid dendritic cells
Original languageRussian
Pages (from-to)653-660
Number of pages8
JournalVavilovskii Zhurnal Genetiki i Selektsii
Volume24
Issue number6
DOIs
Publication statusPublished - 2020

Keywords

  • Allo-mlr
  • Cpg-oligonucleotide
  • Dendritic cells
  • Differentiation
  • Maturation
  • Monocytes
  • Pamp- A nd damp-activators
  • monocytes
  • differentiation
  • allo-MLR
  • CANCER
  • MOTIF
  • maturation
  • dendritic cells
  • PAMP- and DAMP-activators
  • DNA
  • ADJUVANTS
  • TLR9
  • CpG-oligo-nucleotide

OECD FOS+WOS

  • 4 AGRICULTURAL SCIENCES
  • 3 MEDICAL AND HEALTH SCIENCES
  • 1.06 BIOLOGICAL SCIENCES

State classification of scientific and technological information

  • 34 BIOLOGY

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