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通过调节粒细胞-巨噬细胞集落刺激因子、关键炎症细胞因子和转录因子,CD45 细胞参与自闭症谱系障碍的发生。

Involvement of CD45 cells in the development of autism spectrum disorder through dysregulation of granulocyte-macrophage colony-stimulating factor, key inflammatory cytokines, and transcription factors.

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

Int Immunopharmacol. 2020 Jun;83:106466. doi: 10.1016/j.intimp.2020.106466. Epub 2020 Apr 4.

DOI:10.1016/j.intimp.2020.106466
PMID:32259699
Abstract

Autismspectrum disorder (ASD) is a complex and multifactorial heterogeneous disorder. Previous investigations have revealed the association between the immune system and ASD, which is characterized by impaired communication skills. Inflammatory response through CD45 cells plays a key role in the pathogenesis of several autoimmune disorders; however, the molecular mechanism of CD45 cells in ASD is not clearly defined.In this study, we investigated the role of CD45 signaling in children with ASD. In this study, we aimed to investigate the possible involvement of CD45 cells expressing granulocyte-macrophage colony-stimulating factor and inflammatory transcription factors in ASD. Flow cytometric analysis, using peripheral blood mononuclear cells (PBMC), revealed the numbers of GM-CSF-, IFN-γ-, IL-6-, IL-9-, IL-22-, T-bet-, pStat3-, Helios-, and Stat6-producing CD45 cells in children with ASD and children in the control group. We further evaluated the mRNA and protein expression levels of GM-CSF in PBMC by RT-PCR and western blotting analysis. Our results revealed that the children with ASD exhibited significantly higher numbers of CD45GM-CSF, CD45IFN-γ, CD45IL-6, CD45IL-9, CD45IL-22, CD45T-bet, and CD45pStat3 cells compared with the control group. We also found that the children with ASD showed a lower number of CD45Helios and CD45Stat6 cells compared with the control group. Furthermore, the children with ASD showed higher GM-CSF mRNA and protein expression levels compared with the control group. These results indicated that CD45 could play an essential role in the immune abnormalities of ASD. Further investigation of the role of CD45 in neurodevelopment in ASD is warranted.

摘要

自闭症谱系障碍 (ASD) 是一种复杂的、多因素的异质性疾病。先前的研究已经揭示了免疫系统与 ASD 之间的关联,ASD 的特征是沟通能力受损。CD45 细胞的炎症反应在几种自身免疫性疾病的发病机制中起着关键作用;然而,CD45 细胞在 ASD 中的分子机制尚不清楚。在这项研究中,我们研究了 CD45 信号在 ASD 儿童中的作用。在这项研究中,我们旨在研究表达粒细胞-巨噬细胞集落刺激因子和炎症转录因子的 CD45 细胞在 ASD 中的可能作用。使用外周血单核细胞 (PBMC) 的流式细胞术分析显示,ASD 儿童和对照组儿童的 CD45GM-CSF、CD45IFN-γ、CD45IL-6、CD45IL-9、CD45IL-22、CD45T-bet 和 CD45pStat3 产生细胞的数量。我们进一步通过 RT-PCR 和 Western blot 分析评估了 PBMC 中 GM-CSF 的 mRNA 和蛋白表达水平。我们的结果表明,与对照组相比,ASD 儿童的 CD45GM-CSF、CD45IFN-γ、CD45IL-6、CD45IL-9、CD45IL-22、CD45T-bet 和 CD45pStat3 细胞数量显著增加。我们还发现,与对照组相比,ASD 儿童的 CD45Helios 和 CD45Stat6 细胞数量较低。此外,与对照组相比,ASD 儿童的 GM-CSF mRNA 和蛋白表达水平较高。这些结果表明,CD45 在 ASD 的免疫异常中可能发挥重要作用。需要进一步研究 CD45 在 ASD 神经发育中的作用。

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