Dysregulation of Th1, Th2, Th17, and T regulatory cell-related transcription factor signaling in children with autism
Dysregulation of Th1, Th2, Th17, and T regulatory cell-related transcription factor signaling in children with autism
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DOI：
10.1007/s12035-016-9977-0
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发表时间：
2017-08-01
影响因子：
5.1
通讯作者：
Attia, Sabry M.
中科院分区：
文献类型：
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作者：
Ahmad, Sheikh Fayaz;Zoheir, Khairy M. A.;Attia, Sabry M.
自闭症是一种神经发育障碍，其特征是刻板的重复行为、社交障碍和沟通障碍。许多免疫系统异常已被描述为自闭症患者，包括Th1/Th2/Th17细胞比例异常；然而，负责Th1/Th2/Th17/Treg细胞调控和分化的转录因子的表达此前尚未得到评估。在brefeldin a存在的情况下，用phorol -12-肉豆酸盐13-醋酸酯（PMA）和离子霉素刺激自闭症儿童（AU）或正常发育儿童（TD）的外周血单核细胞（PBMCs），评估Foxp3、ROR γ t、STAT-3、t -bet和GATA-3 mrna和蛋白的表达。我们的研究表明，与TD相比，AU患儿表现出免疫特征和功能的改变，其特征是Foxp3(+) T调节（Treg）细胞的系统性缺陷，ROR γ T（+）、T-bet（+）、GATA-3（+）和CD4(+) T细胞的产生增加。实时荧光定量PCR （RT-PCR）和western blot分析证实了这一点。我们的研究结果表明，自闭症影响转录因子信号，从而导致免疫失衡。因此，恢复转录因子信号在自闭症的治疗中可能具有很大的治疗潜力。
Autism is a neurodevelopmental disorder characterized by stereotypic repetitive behaviors, impaired social interactions, and communication deficits. Numerous immune system abnormalities have been described in individuals with autism including abnormalities in the ratio of Th1/Th2/Th17 cells; however, the expression of the transcription factors responsible for the regulation and differentiation of Th1/Th2/Th17/Treg cells has not previously been evaluated. Peripheral blood mononuclear cells (PBMCs) from children with autism (AU) or typically developing (TD) control children were stimulated with phorbol-12-myristate 13-acetate (PMA) and ionomycin in the presence of brefeldin A. The expressions of Foxp3, ROR gamma t, STAT-3, T-bet, and GATA-3 mRNAs and proteins were then assessed. Our study shows that children with AU displayed altered immune profiles and function, characterized by a systemic deficit of Foxp3(+) T regulatory (Treg) cells and increased ROR gamma t(+), T-bet(+), GATA-3(+), and production by CD4(+) T cells as compared to TD. This was confirmed by real-time PCR (RT-PCR) and western blot analyses. Our results suggest that autism impacts transcription factor signaling, which results in an immunological imbalance. Therefore, the restoration of transcription factor signaling may have a great therapeutic potential in the treatment of autistic disorders.