title: The role of programmed cell death ligand-1 (PD-L1/CD274) in the development of graft versus host disease.
abstract: Programmed cell death ligand-1 (PD-L1/CD274) is an immunomodulatory molecule involved in cancer and complications of bone marrow transplantation, such as graft rejection and graft-versus-host disease. The present study was designed to assess the dynamic expression of this molecule after hematopoietic stem cell transplantation in relation to acute graft-versus-host disease. Female BALB/c mice were conditioned with busulfan and cyclophosphamide and transplanted with either syngeneic or allogeneic (male C57BL/6 mice) bone marrow and splenic cells. The expression of PD-L1 was evaluated at different time points employing qPCR, western blot and immunohistochemistry. Allogeneic- but not syngeneic-transplanted animals exhibited a marked up-regulation of PD-L1 expression in the muscle and kidney, but not the liver, at days 5 and 7 post transplantation. In mice transplanted with allogeneic bone marrow cells, the enhanced expression of PD-L1 was associated with high serum levels of IFNγ and TNFα at corresponding intervals. Our findings demonstrate that PD-L1 is differently induced and expressed after allogeneic transplantation than it is after syngeneic transplantation, and that it is in favor of target rather than non-target organs at the early stages of acute graft-versus-host disease. This is the first study to correlate the dynamics of PD-L1 at the gene-, protein- and activity levels with the early development of acute graft-versus-host disease. Our results suggest that the higher expression of PD-L1 in the muscle and kidney (non-target tissues) plays a protective role in skeletal muscle during acute graft-versus-host disease.
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Research Center, Experimental Cancer Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Heevy
authors.initials: H
authors.lastname: Al-Chaqmaqchi
authors.forename: Behnam
authors.initials: B
authors.lastname: Sadeghi
authors.forename: Manuchehr
authors.initials: M
authors.lastname: Abedi-Valugerdi
authors.forename: Sulaiman
authors.initials: S
authors.lastname: Al-Hashmi
authors.forename: Mona
authors.initials: M
authors.lastname: Fares
authors.forename: Raoul
authors.initials: R
authors.lastname: Kuiper
authors.forename: Joachim
authors.initials: J
authors.lastname: Lundahl
authors.forename: Moustapha
authors.initials: M
authors.lastname: Hassan
authors.forename: Ali
authors.initials: A
authors.lastname: Moshfegh
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006086:Graft vs Host Disease / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D060890:B7-H1 Antigen; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma