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白细胞介素(IL)-31 的上调,一种产生 CXCR1 外周免疫细胞的细胞因子,有助于自闭症谱系障碍的免疫异常。

Upregulation of interleukin (IL)-31, a cytokine producing CXCR1 peripheral immune cells, contributes to the immune abnormalities of autism spectrum disorder.

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

J Neuroimmunol. 2020 Dec 15;349:577430. doi: 10.1016/j.jneuroim.2020.577430. Epub 2020 Oct 24.

Abstract

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterized by communication deficits, impaired social interactions, and restricted stereotypical behaviors. Several immune cells are associated with immune dysfunction in ASD; however, IL-31 has not been explored in ASD. This study aims to investigate the role of inflammatory cytokines and transcription factors of the CXCR1 cells in children with ASD. In the current study, we investigated the cytokines and transcription factors produced by CXCR1 cells (IL-31, IL-9, IL-21R, IL-21, NF-κB p65, RORγT, STAT1, and FoxP3) in peripheral blood mononuclear cells (PBMCs), from children with ASD and typically developing (TD) control children, using flow cytometric analysis. In addition, we measured mRNA and protein expression levels of IL-31 using quantitative real-time PCR and western blot analyses in PBMCs. In our study, children with ASD had increased CXCR1IL-31, CXCR1IL-9, CXCR1IL-21R, CXCR1IL-21, CXCR1NF-κB p65, CXCR1RORγT, and CXCR1STAT1, and decreased CXCR1FoxP3 cells as compared with cells from the TD control samples. Similarly, children with ASD showed increased IL-31 mRNA and protein expression levels as compared to those of TD control samples. Our results suggest that upregulated production of inflammatory cytokines and transcription factors in CXCR1 cells cause immunological imbalance in children with ASD. Therefore, attenuation of inflammatory cytokines/mediators and transcription factors could have a therapeutic potential in the treatment of ASD.

摘要

自闭症谱系障碍(ASD)是一组神经发育障碍,其特征为沟通缺陷、社交互动受损和受限刻板行为。几种免疫细胞与 ASD 中的免疫功能障碍有关;然而,IL-31 在 ASD 中尚未得到探索。本研究旨在探讨 CXCR1 细胞中的炎症细胞因子和转录因子在 ASD 儿童中的作用。在本研究中,我们使用流式细胞术分析了 ASD 儿童和典型发育(TD)对照儿童外周血单个核细胞(PBMC)中 CXCR1 细胞产生的细胞因子和转录因子(IL-31、IL-9、IL-21R、IL-21、NF-κB p65、RORγT、STAT1 和 FoxP3)。此外,我们使用定量实时 PCR 和 Western blot 分析测量了 PBMC 中 IL-31 的 mRNA 和蛋白表达水平。在我们的研究中,与 TD 对照样本相比,ASD 儿童的 CXCR1IL-31、CXCR1IL-9、CXCR1IL-21R、CXCR1IL-21、CXCR1NF-κB p65、CXCR1RORγT 和 CXCR1STAT1 细胞增加,而 CXCR1FoxP3 细胞减少。同样,与 TD 对照样本相比,ASD 儿童的 IL-31 mRNA 和蛋白表达水平增加。我们的结果表明,CXCR1 细胞中炎症细胞因子和转录因子的过度产生导致 ASD 儿童的免疫失衡。因此,抑制炎症细胞因子/介质和转录因子可能具有治疗 ASD 的潜力。

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