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Helios 转录因子信号下调与自闭症儿童血液白细胞免疫功能障碍有关。

Downregulation in Helios transcription factor signaling is associated with immune dysfunction in blood leukocytes of autistic children.

机构信息

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

出版信息

Prog Neuropsychopharmacol Biol Psychiatry. 2018 Jul 13;85:98-104. doi: 10.1016/j.pnpbp.2018.04.011. Epub 2018 Apr 23.

DOI:10.1016/j.pnpbp.2018.04.011
PMID:29698674
Abstract

Autism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental disorder in which immunological imbalance has been suggested to be a major etiological component. Helios, a transcription factor, has been studied extensively in the context of human T cell regulation in health and disease, yet the role of Helios signaling has not been examined in children with ASD. In the present study, we investigated the production of Helios in CD4, CD8, and TIM-3, CXCR3 cells in typically developing (TD) controls and children with ASD and in peripheral blood mononuclear cells (PBMCs). We assayed the production of IFN-γHelios, IL-21Helios, T-betHelios, and Foxp3Helios cells, and determined Helios mRNA and protein expression levels in PBMCs, in TD controls and children with ASD. Our results revealed that children with ASD had lower numbers of CD4Helios CD8Helios, TIM-3Helios, and CXCR3Helios cells as compared to TD controls. Our results also showed that children with ASD had decreased IFN-γHelios, IL-21Helios, T-betHelios, and HeliosFoxp3 production compared to that in TD controls. Moreover, our results indicated that children with ASD had lower Helios mRNA and protein expression levels compared to those in TD controls. These results suggest that the Helios transcription factor may be critical to immune alterations in children with ASD. Therefore, our results suggest that targeting Helios signaling might offer a strategy for developing ASD therapies.

摘要

自闭症谱系障碍 (ASD) 是一种复杂的异质性神经发育障碍,其中免疫失衡被认为是主要的发病因素。Helios 是一种转录因子,在健康和疾病中的人类 T 细胞调节中已得到广泛研究,但在 ASD 儿童中尚未研究 Helios 信号的作用。在本研究中,我们研究了典型发育 (TD) 对照组和 ASD 儿童中 CD4、CD8 和 TIM-3、CXCR3 细胞中 Helios 的产生,以及外周血单核细胞 (PBMC) 中的 Helios 信号。我们检测了 IFN-γHelios、IL-21Helios、T-betHelios 和 Foxp3Helios 细胞的产生,并确定了 TD 对照组和 ASD 儿童 PBMC 中的 Helios mRNA 和蛋白表达水平。我们的结果表明,与 TD 对照组相比,ASD 儿童的 CD4Helios CD8Helios、TIM-3Helios 和 CXCR3Helios 细胞数量较少。我们的结果还表明,与 TD 对照组相比,ASD 儿童的 IFN-γHelios、IL-21Helios、T-betHelios 和 HeliosFoxp3 产生减少。此外,我们的结果表明,与 TD 对照组相比,ASD 儿童的 Helios mRNA 和蛋白表达水平较低。这些结果表明,Helios 转录因子可能对 ASD 儿童的免疫改变至关重要。因此,我们的结果表明,靶向 Helios 信号可能为开发 ASD 治疗方法提供策略。

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