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

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）是异基因造血细胞移植后晚期死亡和发病的主要原因，但其发病机制尚不清楚。我们使用定义良好的cGVHD小鼠模型研究了Th亚群在cGVHD中的作用。在该模型中，cGVHD的发展与Th1、Th2和Th17反应上调有关。骨髓移植后早期Th1和Th2反应上调，随后Th17细胞上调。输注IFN-γ(-/-)或IL-17(-/-) T细胞可减弱皮肤和唾液腺的cGVHD。Am80是一种有效的合成类维甲酸，可调节皮肤中Th1和Th17的反应以及TGF-β的表达，从而导致皮肤cGVHD的衰减。这些结果表明，Th1和Th17参与了cGVHD的发展，因此靶向Th1和Th17可能是预防和治疗cGVHD的一种有希望的治疗策略。

项目成果

Synthetic retinoid Am80 ameliorates chronic graft-versus-host disease by downregulating Th1 and Th17

• DOI: 10.4044/joma.124.197
• 发表时间: 2012
• 期刊: Okayama Igakkai Zasshi (journal of Okayama Medical Association)
• 作者: H. Nishimori;Y. Maeda;M. Tanimoto

Donor Th17 and Th1 Contribute to Chronic Graft-Versus-Host Disease

供体 Th17 和 Th1 导致慢性移植物抗宿主病

• 发表时间: 2010
• 作者: Nishimori H;Maeda Y;et al.
• 通讯作者: et al.

Alloantigen expression on non-hematopoietic cells reduces graft-versus-leukemia effects in mice

• DOI: 10.1172/jci39165
• 发表时间: 2010-07-01
• 期刊: JOURNAL OF CLINICAL INVESTIGATION
• 影响因子: 15.9
• 作者: Asakura, Shoji;Hashimoto, Daigo;Teshima, Takanori
• 通讯作者: Teshima, Takanori

合成レチノイドAm80によるTh1/Th17を介した慢性GVHD制御

合成类视黄醇 Am80 控制 Th1/Th17 介导的慢性 GVHD

• 发表时间: 2010
• 作者: 西森久和、前田嘉信;他8名
• 通讯作者: 他8名