Abstract |
Immune checkpoint molecules such as programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) have revolutionized the field of lung cancer treatment. As part of our study, we examined the role of these proteins in acute rejection in a mouse model of heterotopic tracheal transplantation. Recipient mice were untreated (Allo group) or treated with anti-PD-L1 (aPDL1 group) or PD-L1 Fc recombinant protein (PD-L1 Fc group). A further group of C57BL/6 mice received isografts (Iso group). The occlusion rate was significantly higher in the Allo group than in the Iso group (p = 0.0075), and also higher in the aPD-L1 group (p = 0.0066) and lower in the PD-L1 Fc group (p = 0.030) than in the Allo group. PD-L1 Fc recombinant protein treatment significantly decreased interleukin-6 and interferon-γ levels and reduced the CD4+/CD8+ T cell ratio, without increasing PD-1 and T-cell immunoglobulin mucin 3 expression in CD4+ T cells. These data suggest that PD-L1 Fc recombinant protein decreases the levels of inflammatory cytokines and the proportion of CD4+ T cells without exhaustion. The PD-L1-mediated immune checkpoint mechanism was associated with rejection in the murine tracheal transplant model, suggesting a potential novel target for immunotherapy in lung transplantation.
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Authors | Taisuke Kaiho, Hidemi Suzuki, Atsushi Hata, Hiroki Matsumoto, Kazuhisa Tanaka, Yuichi Sakairi, Shinichiro Motohashi, Ichiro Yoshino |
Journal | Frontiers in pharmacology
(Front Pharmacol)
Vol. 14
Pg. 1298085
( 2023)
ISSN: 1663-9812 [Print] Switzerland |
PMID | 38026994
(Publication Type: Journal Article)
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Copyright | Copyright © 2023 Kaiho, Suzuki, Hata, Matsumoto, Tanaka, Sakairi, Motohashi and Yoshino. |