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

研究成果: Article

2 引用 (Scopus)

抄録

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.

元の言語English
ページ(範囲)726-734
ページ数9
ジャーナルSurgery Today
48
発行部数7
DOI
出版物ステータスPublished - 01-07-2018

Fingerprint

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

これを引用

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. :: Surgery Today. 2018 ; 巻 48, 番号 7. pp. 726-734.
@article{9ded7af28eec4a5cb751f61e7e4299dc,
title = "Bone marrow mesenchymal stromal cells protect allograft lung transplants from acute rejection via the PD-L1/IL-17A axis",
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.",
author = "Naoya Ishibashi and Tatsuaki Watanabe and Masahiko Kanehira and Yui Watanabe and Yasushi Hoshikawa and Hirotsugu Notsuda and Masafumi Noda and Akira Sakurada and Shinya Ohkouchi and Takashi Kondo and Yoshinori Okada",
year = "2018",
month = "7",
day = "1",
doi = "10.1007/s00595-018-1643-x",
language = "English",
volume = "48",
pages = "726--734",
journal = "Surgery Today",
issn = "0941-1291",
publisher = "Springer Japan",
number = "7",

}

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, 巻. 48, 番号 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.

:: Surgery Today, 巻 48, 番号 7, 01.07.2018, p. 726-734.

研究成果: Article

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.

UR - http://www.scopus.com/inward/record.url?scp=85044034852&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044034852&partnerID=8YFLogxK

U2 - 10.1007/s00595-018-1643-x

DO - 10.1007/s00595-018-1643-x

M3 - Article

AN - SCOPUS:85044034852

VL - 48

SP - 726

EP - 734

JO - Surgery Today

JF - Surgery Today

SN - 0941-1291

IS - 7

ER -