Imbalance between the anti- and pro-inflammatory milieu in blood leukocytes of autistic children
Imbalance between the anti- and pro-inflammatory milieu in blood leukocytes of autistic children
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DOI：
10.1016/j.molimm.2016.12.019
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发表时间：
2017-02-01
影响因子：
3.6
通讯作者：
Abd-Allah, Adel R. A.
中科院分区：
文献类型：
--
作者：
Ahmad, Sheikh F.;Nadeem, Ahmed;Abd-Allah, Adel R. A.
越来越多的证据表明，免疫功能障碍和自闭症障碍在很大一部分儿童中存在关联。此外，促炎和抗炎通路之间的不平衡已被提出在一些神经发育障碍的发病机制中发挥重要作用，包括自闭症；然而，抗炎分子IL-27和CTLA-4以及促炎细胞因子IL-21和IL-22在自闭症儿童中的作用尚未被探索。在目前的研究中，我们研究了IL-21、IL-22、IL-27和CD152 （CfLA-4）在自闭症儿童（AU）或典型发育儿童（TD）外周血单个核细胞（PBMCs）体外免疫刺激后IL-21、IL-22、IL-27和CD152 （CfLA-4）的表达。在我们的研究中，与来自TD对照的细胞相比，来自AU儿童的细胞在CD4(+) T细胞上IL-21和IL-22的表达增加，CTLA-4的表达降低。同样，与TD对照细胞相比，AU细胞显示CD14（+）细胞产生IL-27的减少。这些结果经实时荧光定量PCR和western blot分析证实。我们的研究表明，自闭症儿童细胞中的免疫平衡失调，表现为促炎细胞因子“IL-21/IL-22”的增强和抗炎分子“IL-27/CTLA-4”的减少。因此，有必要进一步研究自闭症儿童的这种免疫失衡，以促进生物标志物和治疗方法的发展。(C) 2016 Elsevier Ltd.版权所有。
Accumulating evidence suggests an association between immune dysfunction and autism disorders in a significant subset of children. In addition, an imbalance between pro-and anti-inflammatory pathways has been proposed to play an important role in the pathogenesis of several neurodevelopmental disorders including autism; however, the role of anti-inflammatory molecules IL-27 and CTLA-4 and pro-inflammatory cytokines IL-21 and IL-22 has not previously been explored in autistic children. In the current study, we investigated the expression of IL-21, IL-22, IL-27, and CD152 (CfLA-4) following an in vitro immunological challenge of peripheral blood mononuclear cells (PBMCs) from children with autism (AU) or typically-developing children (TD) with phorbol-12-myristate 13-acetate (PMA) and ionomycin. In our study, cells from children with AU had increased IL-21 and IL-22 and decreased CTLA-4 expression on CD4(+) T cells as compared with cells from the TD control. Similarly, AU cells showed decreased IL-27 production by CD14(+) cells compared to that of TD control cells. These results were confirmed by real-time PCR and western blot analyses. Our study shows dysregulation of the immune balance in cells from autistic children as depicted by enhanced pro-inflammatory cytokines, 'IL-21/IL-22' and decreased anti-inflammatory molecules, 'IL-27/CTLA-4'. Thus, further study of this immune imbalance in autistic children is warranted in order to facilitate development of biomarkers and therapeutics. (C) 2016 Elsevier Ltd. All rights reserved.