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围生期因素对早产儿脑损伤中 T 细胞和转录组变化的影响。

Impact of perinatal factors on T cells and transcriptomic changes in preterm infant brain injury.

机构信息

Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, 450052, China.

Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, Shandong, China.

出版信息

J Neuroinflammation. 2024 Nov 29;21(1):310. doi: 10.1186/s12974-024-03311-4.

DOI:10.1186/s12974-024-03311-4
PMID:39614291
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11607874/
Abstract

BACKGROUND

T cells have been implicated in various neurological conditions, yet their role in neonatal brain injuries remains unclear. This study aimed to investigate the impact of perinatal factors on frequencies of T cell subsets in preterm infants and to explore the differences in blood genome expression profiles between preterm infants with and without brain injury.

MATERIALS AND METHODS

Three cohorts of preterm infants were used. Blood samples were collected soon after birth for the first cohort and late timepoint for the second and third cohorts. In the first cohort (88 infants), flow cytometry measured the proportions of αβT and γδT cell subsets in peripheral blood, analyzing associations with gestational age, birth weight, sex, delivery type, and maternal conditions. The second cohort focused on the relationship between T cell subsets and brain injury. In the third cohort, transcriptome sequencing identified differentially expressed genes and pathways in infants with brain injury, highlighting immune-related changes.

RESULTS

Infants born at 29-30 weeks or with a birth weight of 1000-1500 g had significantly higher proportions of Vδ2 T cells compared to those born at 30-32 weeks or with a birth weight > 1500 g, while no significant difference was found between infants born at < 29 weeks or with a birth weight < 1000 g. A negative correlation was observed between gestational age and Vδ2 T cell frequency. No significant associations were found between Vδ2 T cell proportions and perinatal factors other than gestational age or brain injury. Blood transcriptome analysis revealed 173 differentially expressed genes, characterized by downregulated interferon signaling and upregulated antimicrobial and neutrophil pathways in infants with brain injury.

CONCLUSIONS

Gestational age and birth weight influence Vδ2 T cell proportions in preterm infants, likely reflecting immune maturation. While no direct link to brain injury was found, altered immune pathways suggest potential biomarkers for prognosis, warranting further research into their roles and therapeutic implications in neonatal brain injuries.

摘要

背景

T 细胞已被牵涉到各种神经状况中,但其在新生儿脑损伤中的作用仍不清楚。本研究旨在调查围产期因素对早产儿 T 细胞亚群频率的影响,并探讨早产儿有无脑损伤之间血液基因组表达谱的差异。

材料和方法

使用了三个早产儿队列。第一队列在出生后不久采集血液样本,第二和第三队列在晚期采集。在第一队列(88 名婴儿)中,流式细胞术测量了外周血中 αβT 和 γδT 细胞亚群的比例,分析了其与胎龄、出生体重、性别、分娩方式和产妇情况的关联。第二队列重点研究 T 细胞亚群与脑损伤的关系。在第三队列中,转录组测序确定了脑损伤婴儿的差异表达基因和通路,突出了免疫相关的变化。

结果

胎龄为 29-30 周或出生体重为 1000-1500g 的婴儿 Vδ2 T 细胞比例明显高于胎龄为 30-32 周或出生体重>1500g 的婴儿,而胎龄<29 周或出生体重<1000g 的婴儿之间无显著差异。Vδ2 T 细胞频率与胎龄呈负相关。除胎龄或脑损伤外,Vδ2 T 细胞比例与围产期因素之间无显著关联。血液转录组分析显示 173 个差异表达基因,特征为脑损伤婴儿干扰素信号下调和抗菌及中性粒细胞途径上调。

结论

胎龄和出生体重影响早产儿 Vδ2 T 细胞比例,可能反映免疫成熟。虽然未发现与脑损伤直接相关,但免疫途径改变提示可能有预后的生物标志物,需要进一步研究其在新生儿脑损伤中的作用和治疗意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c64/11607874/eaa7e1b36600/12974_2024_3311_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c64/11607874/28a8a67eacd8/12974_2024_3311_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c64/11607874/aabcc499eb25/12974_2024_3311_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c64/11607874/d6f060079232/12974_2024_3311_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c64/11607874/eaa7e1b36600/12974_2024_3311_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c64/11607874/28a8a67eacd8/12974_2024_3311_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c64/11607874/aabcc499eb25/12974_2024_3311_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c64/11607874/d6f060079232/12974_2024_3311_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c64/11607874/eaa7e1b36600/12974_2024_3311_Fig4_HTML.jpg

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