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自闭症儿童肿瘤坏死因子受体-II的差异T细胞水平

Differential T Cell Levels of Tumor Necrosis Factor Receptor-II in Children With Autism.

作者信息

Ashwood Paul

机构信息

Department of Medical Microbiology and Immunology, and The Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, CA, United States.

出版信息

Front Psychiatry. 2018 Nov 20;9:543. doi: 10.3389/fpsyt.2018.00543. eCollection 2018.

Abstract

Autism spectrum disorders (ASD) are characterized by impairments in verbal and non-verbal communication, in social interactions, and often accompanied by stereotypical interests and behaviors. A role for immune dysfunction has long been implicated in ASD pathophysiology, behavioral severity, and co-morbidities. The pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) has been associated with ASD in some studies but little is known about its receptors. There are two receptors for TNFα, with TNFRI relaying many of the signals from TNFα, especially those that are rapid, whilst TNFRII relays later more long-term effects of TNFα. Proteolytic cleavage can lead to the soluble versions of these receptors which can neutralize the effects of TNFα. Here, we determined levels of TNFα and its receptors in 36 children with a confirmed diagnosis of ASD and 27 confirmed typically developing (TD) controls, 2-5 years-of-age. Children with ASD had higher levels of TNFRII on T cells compared to controls following cell stimulation. Levels of sTNFRII were decreased in cell supernatants following stimulation in ASD. Overall these data corroborate the role of inflammatory events in ASD and align with previous studies that have shown differential changes in cellular adaptive immunity in children with ASD. Future longitudinal analyzes of cellular immune function and downstream signaling from immune receptors will help further delineate the role of inflammation in ASD.

摘要

自闭症谱系障碍(ASD)的特征在于言语和非言语交流、社交互动受损,且常伴有刻板的兴趣和行为。免疫功能障碍在ASD的病理生理学、行为严重程度和共病中一直被认为起着一定作用。在一些研究中,促炎细胞因子肿瘤坏死因子α(TNFα)与ASD有关,但其受体的情况却鲜为人知。TNFα有两种受体,其中TNFRI传递许多来自TNFα的信号,尤其是那些快速信号,而TNFRII传递TNFα较晚出现的更长期的效应。蛋白水解切割可导致这些受体的可溶性形式,它们能够中和TNFα的作用。在此,我们测定了36名确诊为ASD的2至5岁儿童以及27名确诊为发育正常(TD)的对照儿童体内TNFα及其受体的水平。与对照相比,ASD儿童在细胞刺激后T细胞上的TNFRII水平更高。在ASD中,刺激后细胞上清液中的可溶性TNFRII(sTNFRII)水平降低。总体而言,这些数据证实了炎症事件在ASD中的作用,并且与之前显示ASD儿童细胞适应性免疫存在差异变化的研究结果一致。未来对细胞免疫功能以及免疫受体下游信号传导的纵向分析将有助于进一步阐明炎症在ASD中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e418/6256095/6930d3af5bb0/fpsyt-09-00543-g0001.jpg

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