AUTHOR=Kaiho Taisuke , Suzuki Hidemi , Hata Atsushi , Matsumoto Hiroki , Tanaka Kazuhisa , Sakairi Yuichi , Motohashi Shinichiro , Yoshino Ichiro 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1298085

DOI=10.3389/fphar.2023.1298085

ISSN=1663-9812

ABSTRACT=<p>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 (<italic>p</italic> = 0.0075), and also higher in the aPD-L1 group (<italic>p</italic> = 0.0066) and lower in the PD-L1 Fc group (<italic>p</italic> = 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<sup>+</sup>/CD8<sup>+</sup> T cell ratio, without increasing PD-1 and T-cell immunoglobulin mucin 3 expression in CD4<sup>+</sup> T cells. These data suggest that PD-L1 Fc recombinant protein decreases the levels of inflammatory cytokines and the proportion of CD4<sup>+</sup> 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.</p>