Targeting PD-1/PD-L1 inhibits rejection in a heterotopic tracheal allograft model of lung transplantation

• Main Authors: Taisuke Kaiho (Author), Hidemi Suzuki (Author), Atsushi Hata (Author), Hiroki Matsumoto (Author), Kazuhisa Tanaka (Author), Yuichi Sakairi (Author), Shinichiro Motohashi (Author), Ichiro Yoshino (Author)
• Format: Book
• Published: Frontiers Media S.A., 2023-11-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

1663-9812
10.3389/fphar.2023.1298085