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Diabetologia:全血先天免疫刺激显示IFN-1在1型糖尿病中反应性高

2020-11-30 MedSci原创 MedSci原创

自身抗原特异性T细胞反应驱动了1型糖尿病的发病机制,但是先天免疫反应的改变也很关键,而且还没有被很好地理解。

自身抗原特异性T细胞反应驱动了1型糖尿病的发病机制,但是先天免疫反应的改变也很关键,而且还没有被很好地理解。人类1型糖尿病的先天免疫主要是通过未受刺激的外周血单核细胞的基因表达分析来评估的,而没有通过免疫激活来放大疾病相关信号。在1型糖尿病中,已经检测到由IFN (IFN-1)或IL-1驱动的两种主要先天免疫途径的应答性增强,但主要的先天免疫途径尚不清楚。本研究旨在确定1型糖尿病的关键先天途径,并评估全血免疫刺激试验作为研究工具。

采用树突培养全血体外刺激试验,结合基因表达和细胞因子测量,来表征1型糖尿病受刺激先天免疫反应的变化。研究人员将特定的细胞因子诱导的特征应用到研究人员的数据中,这些数据是在健康个体的单独队列中测量的相同的分析中预先定义的。另外,用CpG刺激NOD小鼠,测定单核细胞基因表达。

NOD小鼠的单核细胞显示出比糖尿病抗性B6.g7小鼠更低的基线,但诱导的IFN-1相关基因表达更高。在人类受试者中,与健康对照受试者相比,体外全血刺激显示1型糖尿病患者诱导的IFN-1反应较高。相比之下,与健康对照参与者相比,1型糖尿病样本中白细胞介素-1诱导的基因签名或对适应性免疫兴奋剂葡萄球菌肠毒素B的反应都没有显著改变。靶向基因表达分析表明,这种增强的干扰素反应对干扰素-1是特异性的,因为干扰素-γ驱动的反应没有显著差异。

研究发现,对IFN-1的反应增强是NOD小鼠自身免疫性糖尿病模型和人类1型糖尿病模型的一个特征。刺激的IFN-1基因可能是1型糖尿病的潜在生物标志物,并用于评估针对该途径的治疗的效果。

原始出处:

Kameron B. Rodrigues, Matthew J. Dufort,Innate immune stimulation of whole blood reveals IFN-1 hyper-responsiveness in type 1 diabetes

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    2021-08-31 智者为医08
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    2020-12-02 bugit
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    2020-11-30 misszhang

    谢谢MedSci提供最新的资讯

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