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
N1 - Publisher Copyright:
© 2018, Springer Nature Singapore Pte Ltd.
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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U2 - 10.1007/s00595-018-1643-x
DO - 10.1007/s00595-018-1643-x
M3 - Article
C2 - 29546496
AN - SCOPUS:85044034852
SN - 0941-1291
VL - 48
SP - 726
EP - 734
JO - Surgery Today
JF - Surgery Today
IS - 7
ER -