Synthetic Retinoid Am80 Ameliorates Chronic Graft-Versus-Host Disease by Downregulating Th1 and Th17

合成类视黄醇 Am80 通过下调 Th1 和 Th17 改善慢性移植物抗宿主病

• 批准号: 21591244
• 负责人: MAEDA Yoshinobu
• 金额: $ 2.75万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591244/
• 关键词: 同種造血幹細胞移植; 移植片対宿主病; 慢性GVHD; レチノイド; 同種造血幹細胞移植; 移植片対宿主病; 慢性GVHD; レチノイド

Chronic GVHD(cGVHD) is a main cause of late death and morbidity after allogeneic hematopoietic cell transplantation, but its pathogenesis remains unclear. We investigated the roles of Th subsets in cGVHD with the use of a well-defined mouse model of cGVHD. In this model, development of cGVHD was associated with up-regulated Th1, Th2, and Th17 responses. Th1 and Th2 responses were up-regulated early after BM transplantation, followed by a subsequent up-regulation of Th17 cells. Infusion of IFN-γ(-/-) or IL-17(-/-) T cells attenuated cGVHD in the skin and salivary glands. Am80, a potent synthetic retinoid, regulated both Th1 and Th17 responses as well as TGF-βexpression in the skin, resulting in an attenuation of cutaneous cGVHD. These results suggest that Th1 and Th17 contribute to the development of cGVHD and that targeting Th1 and Th17 may therefore represent a promising therapeutic strategy for preventing and treating cGVHD.

慢性GVHD（CGVHD）是同种异体造血细胞移植后死亡和发病率的主要原因，但其发病机理尚不清楚。我们通过使用明确定义的CGVHD模型研究了TH子集在CGVHD中的作用。在该模型中，CGVHD的开发与上调的TH1，TH2和TH17响应有关。 BM移植后，TH1和TH2反应早期上调，然后随后对Th17细胞的上调。输注IFN-γ（ - / - ）或IL-17（ - / - ）T细胞在皮肤和唾液网格中减弱CGVHD。 AM80是一种潜在的合成类维生素类似，调节皮肤中Th1和Th17的反应以及TGF-β表达，导致皮肤CGVHD的衰减。这些结果表明，TH1和TH17有助于CGVHD的发展，因此，针对TH1和TH17的靶向可能代表了预防和治疗CGVHD的承诺的治疗策略。