The Immunomodulatory Effect of Triptolide on Mesenchymal Stromal Cells
Mesenchymal stromal cells (MSCs) are known to have immunosuppressive ability and have been used in clinical treatment of acute graft-versus-host disease, one of severe complications of the hematopoietic stem cell transplantation. However, MSCs are activated to suppress the immune system only after e...
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doaj-71d37c1c9ef04cca95678a1d79093c802021-08-16T09:18:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-08-011210.3389/fimmu.2021.686356686356The Immunomodulatory Effect of Triptolide on Mesenchymal Stromal CellsHaiping He0Haiping He1Atsuko Takahashi2Takeo Mukai3Akiko Hori4Miwako Narita5Arinobu Tojo6Tonghua Yang7Tokiko Nagamura-Inoue8Department of Cell Processing and Transfusion, The Institute of Medical Science, The University of Tokyo, Minato-ku, JapanDepartment of Hematology, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, ChinaDepartment of Cell Processing and Transfusion, The Institute of Medical Science, The University of Tokyo, Minato-ku, JapanDepartment of Cell Processing and Transfusion, The Institute of Medical Science, The University of Tokyo, Minato-ku, JapanDepartment of Cell Processing and Transfusion, The Institute of Medical Science, The University of Tokyo, Minato-ku, JapanLaboratory of Hematology and Oncology, School of Health Science, Niigata University Faculty of Medicine, Niigata, JapanDivision of Molecular Therapy, Center for Advanced Medical Research, Institute of Medical Science, The University of Tokyo, Minato-ku, JapanDepartment of Hematology, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, ChinaDepartment of Cell Processing and Transfusion, The Institute of Medical Science, The University of Tokyo, Minato-ku, JapanMesenchymal stromal cells (MSCs) are known to have immunosuppressive ability and have been used in clinical treatment of acute graft-versus-host disease, one of severe complications of the hematopoietic stem cell transplantation. However, MSCs are activated to suppress the immune system only after encountering an inflammatory stimulation. Thus, it will be ideal if MSCs are primed to be activated and ready to suppress the immune reaction before being administered. Triptolide (TPL) is a diterpene triepoxide purified from a Chinese herb-Tripterygium wilfordii Hook.f. It has been shown to possess anti-inflammatory and immunosuppressive properties in vitro. In this study, we aimed to use TPL to prime umbilical cord-derived MSCs (TPL-primed UC-MSCs) to enter a stronger immunosuppressive status. UC-MSCs were primed with TPL, which was washed out thoroughly, and the TPL-primed UC-MSCs were resuspended in fresh medium. Although TPL inhibited the proliferation of UC-MSCs, 0.01 μM TPL for 24 h was tolerable. The surface markers of TPL-primed UC-MSCs were identical to those of non-primed UC-MSCs. TPL-primed UC-MSCs exhibited stronger anti-proliferative effect for activated CD4+ and CD8+ T cells in the allogeneic mixed lymphocyte reaction assay than the non-primed UC-MSCs. TPL-primed UC-MSCs promoted the expression of IDO-1 in the presence of IFN-γ, but TPL alone was not sufficient. Furthermore, TPL-primed UC-MSCs showed increased expression of PD-L1. Conclusively, upregulation of IDO-1 in the presence of IFN-γ and induction of PD-L1 enhances the immunosuppressive potency of TPL-primed UC-MSCs on the proliferation of activated T cells. Thus, TPL- primed MSCs may provide a novel immunosuppressive cell therapy.https://www.frontiersin.org/articles/10.3389/fimmu.2021.686356/fullmesenchymal stromal cellsumbilical cordtriptolideimmunosuppressionPD-L1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Haiping He Haiping He Atsuko Takahashi Takeo Mukai Akiko Hori Miwako Narita Arinobu Tojo Tonghua Yang Tokiko Nagamura-Inoue |
spellingShingle |
Haiping He Haiping He Atsuko Takahashi Takeo Mukai Akiko Hori Miwako Narita Arinobu Tojo Tonghua Yang Tokiko Nagamura-Inoue The Immunomodulatory Effect of Triptolide on Mesenchymal Stromal Cells Frontiers in Immunology mesenchymal stromal cells umbilical cord triptolide immunosuppression PD-L1 |
author_facet |
Haiping He Haiping He Atsuko Takahashi Takeo Mukai Akiko Hori Miwako Narita Arinobu Tojo Tonghua Yang Tokiko Nagamura-Inoue |
author_sort |
Haiping He |
title |
The Immunomodulatory Effect of Triptolide on Mesenchymal Stromal Cells |
title_short |
The Immunomodulatory Effect of Triptolide on Mesenchymal Stromal Cells |
title_full |
The Immunomodulatory Effect of Triptolide on Mesenchymal Stromal Cells |
title_fullStr |
The Immunomodulatory Effect of Triptolide on Mesenchymal Stromal Cells |
title_full_unstemmed |
The Immunomodulatory Effect of Triptolide on Mesenchymal Stromal Cells |
title_sort |
immunomodulatory effect of triptolide on mesenchymal stromal cells |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2021-08-01 |
description |
Mesenchymal stromal cells (MSCs) are known to have immunosuppressive ability and have been used in clinical treatment of acute graft-versus-host disease, one of severe complications of the hematopoietic stem cell transplantation. However, MSCs are activated to suppress the immune system only after encountering an inflammatory stimulation. Thus, it will be ideal if MSCs are primed to be activated and ready to suppress the immune reaction before being administered. Triptolide (TPL) is a diterpene triepoxide purified from a Chinese herb-Tripterygium wilfordii Hook.f. It has been shown to possess anti-inflammatory and immunosuppressive properties in vitro. In this study, we aimed to use TPL to prime umbilical cord-derived MSCs (TPL-primed UC-MSCs) to enter a stronger immunosuppressive status. UC-MSCs were primed with TPL, which was washed out thoroughly, and the TPL-primed UC-MSCs were resuspended in fresh medium. Although TPL inhibited the proliferation of UC-MSCs, 0.01 μM TPL for 24 h was tolerable. The surface markers of TPL-primed UC-MSCs were identical to those of non-primed UC-MSCs. TPL-primed UC-MSCs exhibited stronger anti-proliferative effect for activated CD4+ and CD8+ T cells in the allogeneic mixed lymphocyte reaction assay than the non-primed UC-MSCs. TPL-primed UC-MSCs promoted the expression of IDO-1 in the presence of IFN-γ, but TPL alone was not sufficient. Furthermore, TPL-primed UC-MSCs showed increased expression of PD-L1. Conclusively, upregulation of IDO-1 in the presence of IFN-γ and induction of PD-L1 enhances the immunosuppressive potency of TPL-primed UC-MSCs on the proliferation of activated T cells. Thus, TPL- primed MSCs may provide a novel immunosuppressive cell therapy. |
topic |
mesenchymal stromal cells umbilical cord triptolide immunosuppression PD-L1 |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2021.686356/full |
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