Westphal Sabine, McGeary Aleixandria, Rudloff Sandra, Wilke Andrea, Penack Olaf
Department of Hematology, Oncology and Tumorimmunology, Charité Campus Virchow, Berlin, Germany.
PLoS One. 2017 Jan 19;12(1):e0169630. doi: 10.1371/journal.pone.0169630. eCollection 2017.
Allogeneic hematopoetic stem cell transplantation (allo-HSCT) is a standard treatment for leukemia and other hematologic malignancies. The major complication of allo-HSCT is graft-versus-host-disease (GVHD), a progressive inflammatory illness characterized by donor immune cells attacking the organs of the recipient. Current GVHD prevention and treatment strategies use immune suppressive drugs and/or anti-T cell reagents these can lead to increased risk of infections and tumor relapse. Recent research demonstrated that epigallocatechin gallate (EGCG), a component found in green tea leaves at a level of 25-35% at dry weight, may be useful in the inhibition of GVHD due to its immune modulatory, anti-oxidative and anti-angiogenic capacities. In murine allo-HSCT recipients treated with EGCG, we found significantly reduced GVHD scores, reduced target organ GVHD and improved survival. EGCG treated allo-HSCT recipients had significantly higher numbers of regulatory T cells in GVHD target organs and in the blood. Furthermore, EGCG treatment resulted in diminished oxidative stress indicated by significant changes of glutathione blood levels as well as glutathione peroxidase in the colon. In summary, our study provides novel evidence demonstrating that EGCG ameliorates lethal GVHD and reduces GVHD-related target organ damage. Possible mechanisms are increased regulatory T cell numbers and reduced oxidative stress.
异基因造血干细胞移植（allo-HSCT）是白血病和其他血液系统恶性肿瘤的标准治疗方法。allo-HSCT的主要并发症是移植物抗宿主病（GVHD），这是一种进行性炎症性疾病，其特征是供体免疫细胞攻击受体的器官。目前的GVHD预防和治疗策略使用免疫抑制药物和/或抗T细胞试剂，这些可能会导致感染和肿瘤复发风险增加。最近的研究表明，表没食子儿茶素没食子酸酯（EGCG），一种在干重含量为25-35%的绿茶中发现的成分，因其免疫调节、抗氧化和抗血管生成能力，可能对抑制GVHD有用。在用EGCG治疗的小鼠allo-HSCT受体中，我们发现GVHD评分显著降低，靶器官GVHD减轻，存活率提高。经EGCG治疗的allo-HSCT受体在GVHD靶器官和血液中的调节性T细胞数量显著增加。此外，EGCG治疗导致氧化应激减轻，这表现为结肠中谷胱甘肽血水平以及谷胱甘肽过氧化物酶的显著变化。总之，我们的研究提供了新的证据，证明EGCG可改善致命的GVHD并减少GVHD相关的靶器官损伤。可能的机制是调节性T细胞数量增加和氧化应激减轻。
