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急性动脉瘤性蛛网膜下腔出血中免疫微环境的调节:单核细胞通过分泌CXCL10的潜在作用。

Modulation of the Immunological Milieu in Acute Aneurysmal Subarachnoid Hemorrhage: The Potential Role of Monocytes Through CXCL10 Secretion.

作者信息

Sanchez Sebastian, Chimenti Michael S, Lu Yongjun, Sagues Elena, Gudino Andres, Dier Carlos, Hasan David, Samaniego Edgar A

机构信息

Department of Neurology, Yale University, New Haven, CT, USA.

Iowa Institute of Human Genetics, University of Iowa, Iowa, IA, USA.

出版信息

Transl Stroke Res. 2025 Feb;16(1):88-95. doi: 10.1007/s12975-024-01259-4. Epub 2024 May 23.

Abstract

Emerging evidence indicates that aneurysmal subarachnoid hemorrhage (aSAH) elicits a response from both innate and adaptive immune systems. An upregulation of CD8 + CD161 + cells has been observed in the cerebrospinal fluid (CSF) after aSAH, yet the precise role of these cells in the context of aSAH is unkown. CSF samples from patients with aSAH and non-aneurysmal SAH (naSAH) were analyzed. Single-cell RNA sequencing (scRNAseq) was performed on CD8 + CD161 + sorted samples from aSAH patients. Cell populations were identified using "clustering." Gene expression levels of ten previously described genes involved in inflammation were quantified from aSAH and naSAH samples using RT-qPCR. The study focused on the following genes: CCL5, CCL7, APOE, SPP1, CXCL8, CXCL10, HMOX1, LTB, MAL, and HLA-DRB1. Gene clustering analysis revealed that monocytes, NK cells, and T cells expressed CD8 + CD161 + in the CSF of patients with aSAH. In comparison to naSAH samples, aSAH samples exhibited higher mRNA levels of CXCL10 (median, IQR = 90, 16-149 vs. 0.5, 0-6.75, p = 0.02). A trend towards higher HMOX1 levels was also observed in aSAH (median, IQR = 12.6, 9-17.6 vs. 2.55, 1.68-5.7, p = 0.076). Specifically, CXCL10 and HMOX1 were expressed by the monocyte subpopulation. Monocytes, NK cells, and T cells can potentially express CD8 + CD161 + in patients with aSAH. Notably, monocytes show high levels of CXCL10. The elevated expression of CXCL10 in aSAH compared to naSAH indicates its potential significance as a target for future studies.

摘要

新出现的证据表明,动脉瘤性蛛网膜下腔出血(aSAH)会引发先天性和适应性免疫系统的反应。aSAH后,脑脊液(CSF)中观察到CD8+CD161+细胞上调,但这些细胞在aSAH背景下的确切作用尚不清楚。分析了aSAH患者和非动脉瘤性SAH(naSAH)患者的脑脊液样本。对aSAH患者的CD8+CD161+分选样本进行了单细胞RNA测序(scRNAseq)。使用“聚类”识别细胞群体。使用RT-qPCR从aSAH和naSAH样本中定量先前描述的十个参与炎症的基因的基因表达水平。该研究重点关注以下基因:CCL5、CCL7、APOE、SPP1、CXCL8、CXCL10、HMOX1、LTB、MAL和HLA-DRB1。基因聚类分析显示,单核细胞、NK细胞和T细胞在aSAH患者的脑脊液中表达CD8+CD161+。与naSAH样本相比,aSAH样本中CXCL10的mRNA水平更高(中位数,IQR = 90, 16 - 149 vs. 0.5, 0 - 6.75,p = 0.02)。在aSAH中也观察到HMOX1水平有升高趋势(中位数,IQR = 12.6, 9 - 17.6 vs. 2.55, 1.68 - 5.7,p = 0.076)。具体而言,CXCL10和HMOX1由单核细胞亚群表达。在aSAH患者中,单核细胞、NK细胞和T细胞可能表达CD8+CD161+。值得注意的是,单核细胞显示出高水平的CXCL10。与naSAH相比,aSAH中CXCL10的表达升高表明其作为未来研究靶点的潜在意义。

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