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.
Prog Neuropsychopharmacol Biol Psychiatry. 2017 Oct 3;79(Pt B):472-480. doi: 10.1016/j.pnpbp.2017.08.002. Epub 2017 Aug 9.
Autism spectrum disorder (ASD) gradually develops predominantly neurodevelopmental disorders, which are socially diagnosed in early childhood. Though the etiopathology of ASD is not clear, immune alteration has been suggested as autism's pathophysiological mechanism. Previous studies found that several cytokines and transcription factor activation pathways were significantly increased in ASD. IL-9 has been confirmed to play a significant role in the central nervous system (CNS). The aim of the present study was to investigate the understudied role of pro- and anti-inflammatory cytokines and the JAK-STAT signaling pathway in ASD. We examined the IL-1β, IL-4, IFN-γ, and IL-9 positive immunostaining in all cells, and CD4 T cells, in ASD and normally developing control children (TD), on peripheral blood mononuclear cells (PBMCs), using flow cytometry. We explored PBMC mRNA expression levels for IL-1β, IL-4, IFN-γ, IL-9, JAK1, and STAT5, by using real-time PCR (RT-PCR). We also explored PBMC protein expression levels for IL-1β, IL-4, IL-9, pJAK1, and pSTAT5 by using western blotting. We found that the children with ASD had increased IL-1β, IL-4, IFN-γ, and IL-9 positive immunostaining in all cells, and in CD4 cells, relative to the TD controls. The mRNA and protein expression for IL-1β, IL-4, IFN-γ, IL-9, JAK1, pJAK1, STAT5, and pSTAT5 were also significantly elevated in ASD relative to TD controls. These results suggested that cytokines and JAK-STAT activation signaling have an essential role in immune dysfunction in ASD.
自闭症谱系障碍（ASD）逐渐发展为主要的神经发育障碍，在儿童早期被社会诊断出来。尽管 ASD 的病因病理尚不清楚，但免疫改变已被认为是自闭症的病理生理机制。先前的研究发现，自闭症患者体内几种细胞因子和转录因子激活途径显著增加。IL-9 已被证实在中枢神经系统（CNS）中发挥重要作用。本研究旨在探讨促炎和抗炎细胞因子以及 JAK-STAT 信号通路在 ASD 中的作用。我们使用流式细胞术检查了 ASD 和正常发育对照儿童（TD）外周血单个核细胞（PBMC）中所有细胞和 CD4 T 细胞中 IL-1β、IL-4、IFN-γ 和 IL-9 的阳性免疫染色。我们通过实时 PCR（RT-PCR）探索了 PBMC 中 IL-1β、IL-4、IFN-γ、IL-9、JAK1 和 STAT5 的 mRNA 表达水平。我们还通过 Western blot 探索了 PBMC 中 IL-1β、IL-4、IL-9、pJAK1 和 pSTAT5 的蛋白表达水平。我们发现，与 TD 对照组相比，ASD 患儿的所有细胞和 CD4 细胞中的 IL-1β、IL-4、IFN-γ 和 IL-9 阳性免疫染色均增加。与 TD 对照组相比，ASD 患者的 IL-1β、IL-4、IFN-γ、IL-9、JAK1、pJAK1、STAT5 和 pSTAT5 的 mRNA 和蛋白表达也显著升高。这些结果表明，细胞因子和 JAK-STAT 激活信号在 ASD 中的免疫功能障碍中起着重要作用。
