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

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 int...

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Bibliographic Details
Published in:Surgery today (Tokyo, Japan) Japan), 2018-07, Vol.48 (7), p.726-734
Main Authors: Ishibashi, Naoya, Watanabe, Tatsuaki, Kanehira, Masahiko, Watanabe, Yui, Hoshikawa, Yasushi, Notsuda, Hirotsugu, Noda, Masafumi, Sakurada, Akira, Ohkouchi, Shinya, Kondo, Takashi, Okada, Yoshinori
Format: Article
Language:English
Subjects:
Acute Disease
Allografts
Animals
B7-H1 Antigen - genetics
B7-H1 Antigen - metabolism
Bone Marrow Cells
Down-Regulation
Gene Expression
Graft Rejection - prevention & control
Interleukin-17 - genetics
Interleukin-17 - metabolism
Lung Transplantation
Male
Medicine
Medicine & Public Health
Mesenchymal Stem Cells
Models, Animal
Original Article
Rats
Rats, Inbred Lew
RNA, Messenger - genetics
RNA, Messenger - metabolism
Surgery
Surgical Oncology
T-Lymphocytes - immunology
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Summary: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.
ISSN:0941-1291
1436-2813
DOI:10.1007/s00595-018-1643-x