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

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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

All Science Journal Classification (ASJC) codes

  • Surgery

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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, 48(7), 726-734. https://doi.org/10.1007/s00595-018-1643-x