Synthetic retinoid Am80 ameliorates chronic graft-versus-host disease by down-regulating Th1 and Th17
Synthetic retinoid Am80 ameliorates chronic graft-versus-host disease by down-regulating Th1 and Th17
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DOI：
10.1182/blood-2011-01-332478
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发表时间：
2012-01-05
期刊：
影响因子：
20.3
通讯作者：
Tanimoto, Mitsune
中科院分区：
文献类型：
--
作者：
Nishimori, Hisakazu;Maeda, Yoshinobu;Tanimoto, Mitsune
慢性移植物抗宿主病（cGVHD）是异基因造血细胞移植后晚期死亡和并发症的主要原因，但其发病机制尚不清楚。我们研究了Th亚群在cGVHD中的作用，使用一个明确的小鼠cGVHD模型。在该模型中，cGVHD的发生与Th 1、Th 2和Th 17应答上调相关。骨髓移植后早期Th 1和Th 2应答上调，随后Th 17细胞上调。同种异体受者的肺和肝中浸润的Th 17细胞数量显著高于同系受者。然后，我们使用IFN-γ缺陷型和IL-17缺陷型小鼠作为供体，评估了Th 1和Th 17在cGVHD中的作用。输注IFN-γ（-/-）或IL-17（-/-）T细胞减弱皮肤和唾液腺中的cGVHD。Am 80是一种有效的合成类维生素A，可调节皮肤中的Th 1和Th 17反应以及TGF-β表达，从而减弱皮肤cGVHD。这些结果表明，Th 1和Th 17有助于cGVHD的发展，因此，靶向Th 1和Th 17可能代表预防和治疗cGVHD的有希望的治疗策略。（血。2012; 119（1）：285-295）
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. Significantly greater numbers of Th17 cells were infiltrated in the lung and liver from allogeneic recipients than those from syngeneic recipients. We then evaluated the roles of Th1 and Th17 in cGVHD with the use of IFN-gamma-deficient and IL-17-deficient mice as donors. Infusion of IFN-gamma(-/-) 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-beta expression 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. (Blood. 2012; 119(1): 285-295)