Odabas, Gul PelinAslan, KubraSuna, Pinar AlisanKendirli, Perihan KaderErdem, ŞerifeÇakır, MustafaÖzcan, AlperYılmaz, EbruKarakukcu, MusaDonmez-Altuntas, HamiyetYay, Arzu HanimDeniz, KemalAltay, DeryaArslan, DuranCanatan, HalitEken, AhmetUnal, Ekrem2024-02-262024-02-26202415675769https://doi.org/10.1016/j.intimp.2024.111560https://hdl.handle.net/20.500.12573/1961The anti-inflammatory and immunosuppressive drugs which are used in the treatment of Graft-versus-Host Disease (GVHD) have limited effects in controlling the severity of the disease. In this study, we aimed to investigate the prophylactic effect of Alantolactone (ALT) in a murine model of experimental GVHD. The study included 4 BALB/c groups as hosts: Naïve (n = 7), Control GVHD (n = 16), ALT-GVHD (n = 16), and Syngeneic transplantation (n = 10). Busulfan (20 mg/kg/day) for 4 days followed by cyclophosphamide (100 mg/kg/day) were administered for conditioning. Allogeneic transplantation was performed with cells collected from mismatched female C57BL/6, and GVHD development was monitored by histological and flow cytometric assays. Additionally, liver biopsies were taken from GVHD patient volunteers between ages 2–18 (n = 4) and non-GVHD patients between ages 2–50 (n = 5) and cultured ex vivo with ALT, and the supernatants were used for ELISA. ALT significantly ameliorated histopathological scores of the GVHD and improved GVHD clinical scores. CD8+ T cells were shown to be reduced after ALT treatment. More importantly, ALT treatment skewed T cells to a more naïve phenotype (CD62L+ CD44− ). ALT did not alter Treg cell number or frequency. ALT treatment appears to suppress myeloid cell lineage (CD11c+). Consistent with reduced myeloid lineage, liver and small intestine levels of GM-CSF were reduced in ALT-treated mice. IL-6 gene expression was significantly reduced in the intestinal tissue. Ex vivo ALT-treated liver biopsy samples from GVHD patients showed a trend of decrease in proinflammatory cytokines but there was no statistical significance. Collectively, the data indicated that ALT may have immunomodulatory actions in a preclinical murine GVHD model.enginfo:eu-repo/semantics/closedAccessAlantolactoneGraft versus host diseaseBone marrow transplantationAllogenic transplantationAutoimmunityarticle12818