Blood:小肠类器官成功重现对T细胞介导的组织损伤的易感性

2020-04-04 MedSci原创 MedSci原创

在Atg16L1缺陷小鼠中,通过抑制坏死作用可逆转肠内GVHD。 体内外结合类器官和T细胞的平台可以重建对组织损伤的易感性,并可应用于药物测试。

精准医疗的一个目标是利用患者提供的材料来预测疾病过程和干预结果。

在本研究中,Ishimoto等人在预临床动物模型中使用机械观察设计了一个体外平台,以重建对T细胞介导损伤的遗传易感性。

肠移植物抗宿主病(GVHD)是异基因造血细胞移植(allo-HCT)的一种危及生命的并发症。Ishimoto等人发现,在Atg16L1(一种多态自噬基因)缺陷小鼠中,肠内GVHD可通过抑制坏死作用而得以逆转。

此外,研究人员还发现,异基因T细胞共培养可杀伤小鼠来源的Atg16L1突变的小肠类器官,这与上皮干扰素信号异常有关。

利用这些信息,研究人员证明了从药物抑制坏死作用或干扰素信号转导可以保护来自携带常见ATG16L1变异个体的人的类器官免受异基因T细胞攻击。

综上所述,本研究为将在动物模型上的研究发现应用于针对受影响组织的个体化治疗提供了一种新思路。

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