Gingerol Ameliorates Chronic Graft-Versus-Host Disease by Regulating Treg/Th17 Transdifferentiation

The study investigates the effects of gingerol on chronic graft-versus-host disease (cGVHD) using two mouse models. Gingerol was administered orally, leading to improved survival rates, reduced body weight loss, and lower clinical cGVHD scores. Histopathological analysis showed decreased tissue damage in the liver, lung, and gastrointestinal tract. Gingerol treatment reduced pro-inflammatory cytokines and altered T cell populations by decreasing TNF-α+, IFN-γ+, and IL-17+ T cells while increasing Foxp3+CD4+ T cells. RNA sequencing revealed that gingerol suppresses the P2RY13 receptor, which was confirmed by flow cytometry. Additionally, gingerol upregulated inhibitory receptors CD244 and PD-1 on T cells, suggesting a mechanism for its therapeutic effects. The study concludes that gingerol acts as a P2RY13 antagonist, offering potential as a treatment for steroid-refractory cGVHD by modulating T cell activation and differentiation.