1. Analysis of therapeutic potential of monocytic myeloid-derived suppressor cells in cardiac allotransplantation.
- Author
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Fujimoto K, Uchida K, Yin E, Zhu J, Kojima Y, Uchiyama M, Yamamoto Y, Bashuda H, Matsumoto R, Tokushige K, Harada M, Inomata T, Kitaura J, Murakami A, Okumura K, and Takeda K
- Subjects
- Adoptive Transfer, Animals, Cells, Cultured, Disease Models, Animal, Graft Survival, Humans, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Myeloid-Derived Suppressor Cells transplantation, Nitric Oxide Synthase Type II metabolism, Transplantation, Homologous, Graft Rejection therapy, Heart Transplantation, Immunosuppression Therapy methods, Monocytes immunology, Myeloid-Derived Suppressor Cells immunology, T-Lymphocytes, Regulatory immunology
- Abstract
Background: Myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) are attractive immune cells to induce immune tolerance. To explore a strategy for improving the efficacy of MDSC therapies, we examined the impact of adoptive transfer of several types of MDSCs on graft rejection in a murine heart transplantation model., Methods: We analyzed the effects of induced syngeneic and allogeneic bone marrow-derived MDSCs (BM-MDSCs) on graft survival and suppressive capacity. We also compared the ability of syngeneic monocytic MDSCs (Mo-MDSCs) and polymorphonuclear MDSCs (PMN-MDSCs) to inhibit graft rejection and investigated the suppression mechanisms., Results: Both syngeneic and allogeneic donor- or allogeneic third-party-derived BM-MDSCs prolonged graft survival, although syngeneic BM-MDSCs inhibited anti-donor immune responses most effectively in vitro. Syngeneic Mo-MDSCs, rather than PMN-MDSCs, were responsible for immune suppression through downregulating inducible nitric oxide synthase (iNOS) and expanded naturally occurring thymic originated Treg (nTreg) in vitro. Adoptive transfer of Mo-MDSCs, but not PMN-MDSCs, prolonged graft survival and increased Treg infiltration into the graft heart., Conclusion: Recipient-derived Mo-MDSCs are most effective in prolonging graft survival via inhibiting T cell response and nTreg infiltration., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2021
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