Bone marrow mesenchymal stromal cells protect allograft lung transplants from acute rejection via the PD-L1/IL-17A axis

Naoya Ishibashi, Tatsuaki Watanabe, Masahiko Kanehira, Yui Watanabe, Yasushi Hoshikawa, Hirotsugu Notsuda, Masafumi Noda, Akira Sakurada, Shinya Ohkouchi, Takashi Kondo, Yoshinori Okada

Research output: Contribution to journalArticle

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Abstract

Purpose: Using a rat model of allograft lung transplantation, we investigated the effectiveness of mesenchymal stromal cells (MSCs) as prophylactic and therapeutic agents against the acute rejection of lung grafts. Methods: Lung grafts were harvested from donor rats and transplanted orthotopically into major histocompatibility complex-mismatched rats. MSCs were administered to the recipients once (on day 0) or twice (on days 0 and 3) after transplantation. The grade of acute rejection was evaluated both macroscopically and microscopically 6 days after transplantation. To elucidate the related mechanism, mRNA levels of inflammatory cytokines and immunomodulatory receptors in the transplanted grafts were measured using quantitative RT-PCR. Results: The lung graft tissue from the rats that received MSCs post-surgically was protected from acute rejection significantly better than that from the untreated controls. Notably, the rats administered MSCs twice after surgery exhibited the least signs of rejection, with a markedly upregulated mRNA level of PD-L1 and a downregulated mRNA level of IL-17A. Conclusion: This study assessed MSC protection of lung allografts from acute rejection by modulating T cell activity via enforced expression of PD-L1 in transplants and downregulation of IL-17A.

Original languageEnglish
Pages (from-to)726-734
Number of pages9
JournalSurgery Today
Volume48
Issue number7
DOIs
Publication statusPublished - 01-07-2018

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Interleukin-17
Graft Rejection
Mesenchymal Stromal Cells
Allografts
Lung
Transplants
Messenger RNA
Down-Regulation
Transplantation
Cytokine Receptors
Cytoprotection
Lung Transplantation
Major Histocompatibility Complex
T-Lymphocytes
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

Ishibashi, Naoya ; Watanabe, Tatsuaki ; Kanehira, Masahiko ; Watanabe, Yui ; Hoshikawa, Yasushi ; Notsuda, Hirotsugu ; Noda, Masafumi ; Sakurada, Akira ; Ohkouchi, Shinya ; Kondo, Takashi ; Okada, Yoshinori. / Bone marrow mesenchymal stromal cells protect allograft lung transplants from acute rejection via the PD-L1/IL-17A axis. In: Surgery Today. 2018 ; Vol. 48, No. 7. pp. 726-734.
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abstract = "Purpose: Using a rat model of allograft lung transplantation, we investigated the effectiveness of mesenchymal stromal cells (MSCs) as prophylactic and therapeutic agents against the acute rejection of lung grafts. Methods: Lung grafts were harvested from donor rats and transplanted orthotopically into major histocompatibility complex-mismatched rats. MSCs were administered to the recipients once (on day 0) or twice (on days 0 and 3) after transplantation. The grade of acute rejection was evaluated both macroscopically and microscopically 6 days after transplantation. To elucidate the related mechanism, mRNA levels of inflammatory cytokines and immunomodulatory receptors in the transplanted grafts were measured using quantitative RT-PCR. Results: The lung graft tissue from the rats that received MSCs post-surgically was protected from acute rejection significantly better than that from the untreated controls. Notably, the rats administered MSCs twice after surgery exhibited the least signs of rejection, with a markedly upregulated mRNA level of PD-L1 and a downregulated mRNA level of IL-17A. Conclusion: This study assessed MSC protection of lung allografts from acute rejection by modulating T cell activity via enforced expression of PD-L1 in transplants and downregulation of IL-17A.",
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Ishibashi, N, Watanabe, T, Kanehira, M, Watanabe, Y, Hoshikawa, Y, Notsuda, H, Noda, M, Sakurada, A, Ohkouchi, S, Kondo, T & Okada, Y 2018, 'Bone marrow mesenchymal stromal cells protect allograft lung transplants from acute rejection via the PD-L1/IL-17A axis', Surgery Today, vol. 48, no. 7, pp. 726-734. https://doi.org/10.1007/s00595-018-1643-x

Bone marrow mesenchymal stromal cells protect allograft lung transplants from acute rejection via the PD-L1/IL-17A axis. / Ishibashi, Naoya; Watanabe, Tatsuaki; Kanehira, Masahiko; Watanabe, Yui; Hoshikawa, Yasushi; Notsuda, Hirotsugu; Noda, Masafumi; Sakurada, Akira; Ohkouchi, Shinya; Kondo, Takashi; Okada, Yoshinori.

In: Surgery Today, Vol. 48, No. 7, 01.07.2018, p. 726-734.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Bone marrow mesenchymal stromal cells protect allograft lung transplants from acute rejection via the PD-L1/IL-17A axis

AU - Ishibashi, Naoya

AU - Watanabe, Tatsuaki

AU - Kanehira, Masahiko

AU - Watanabe, Yui

AU - Hoshikawa, Yasushi

AU - Notsuda, Hirotsugu

AU - Noda, Masafumi

AU - Sakurada, Akira

AU - Ohkouchi, Shinya

AU - Kondo, Takashi

AU - Okada, Yoshinori

PY - 2018/7/1

Y1 - 2018/7/1

N2 - Purpose: Using a rat model of allograft lung transplantation, we investigated the effectiveness of mesenchymal stromal cells (MSCs) as prophylactic and therapeutic agents against the acute rejection of lung grafts. Methods: Lung grafts were harvested from donor rats and transplanted orthotopically into major histocompatibility complex-mismatched rats. MSCs were administered to the recipients once (on day 0) or twice (on days 0 and 3) after transplantation. The grade of acute rejection was evaluated both macroscopically and microscopically 6 days after transplantation. To elucidate the related mechanism, mRNA levels of inflammatory cytokines and immunomodulatory receptors in the transplanted grafts were measured using quantitative RT-PCR. Results: The lung graft tissue from the rats that received MSCs post-surgically was protected from acute rejection significantly better than that from the untreated controls. Notably, the rats administered MSCs twice after surgery exhibited the least signs of rejection, with a markedly upregulated mRNA level of PD-L1 and a downregulated mRNA level of IL-17A. Conclusion: This study assessed MSC protection of lung allografts from acute rejection by modulating T cell activity via enforced expression of PD-L1 in transplants and downregulation of IL-17A.

AB - Purpose: Using a rat model of allograft lung transplantation, we investigated the effectiveness of mesenchymal stromal cells (MSCs) as prophylactic and therapeutic agents against the acute rejection of lung grafts. Methods: Lung grafts were harvested from donor rats and transplanted orthotopically into major histocompatibility complex-mismatched rats. MSCs were administered to the recipients once (on day 0) or twice (on days 0 and 3) after transplantation. The grade of acute rejection was evaluated both macroscopically and microscopically 6 days after transplantation. To elucidate the related mechanism, mRNA levels of inflammatory cytokines and immunomodulatory receptors in the transplanted grafts were measured using quantitative RT-PCR. Results: The lung graft tissue from the rats that received MSCs post-surgically was protected from acute rejection significantly better than that from the untreated controls. Notably, the rats administered MSCs twice after surgery exhibited the least signs of rejection, with a markedly upregulated mRNA level of PD-L1 and a downregulated mRNA level of IL-17A. Conclusion: This study assessed MSC protection of lung allografts from acute rejection by modulating T cell activity via enforced expression of PD-L1 in transplants and downregulation of IL-17A.

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