Transcriptomic dose-response by UVC and heavy ion radiation reveal pathways to immune impairment

IF 2.6 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro Pub Date : 2025-05-24 DOI:10.1016/j.tiv.2025.106086

Mingming Tian , Xiaolin Ding , Yue Pang , Dan Xu , Yeqing Sun , Pu Xia

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引用次数: 0

Abstract

Irradiation-induced immune impairment has been linked to human immune diseases, such as myelodysplastic syndromes (MDS) and leukemia. Global molecular responses to genome instability in immune cells can be identified by using transcriptomics. However, it is hard to link the molecular mechanism to the disease outcomes in the previous mechanistic studies. Here, transcriptomic dose-responses in human CD4+ T lymphocytes exposed to ultraviolet and heavy ion radiation were revealed by identification of the gene expression patterns of differential expression genes (DEGs) and calculating the point of departure (POD) of each DEG and molecular pathway, which provided an opportunity for quantitively illustrating the biological process of irradiation-induced immune impairments. Two potential adverse outcome pathways (AOPs) to irradiation-related leukemia were identified by mapping the molecular pathways into the biological event cascades, which provided phenotypic anchoring for the toxicological mechanisms. In addition, this study also revealed that NOP14/ NOP14-AS1 could be potential biomarkers of irradiation-induced immune impairment. Our works strengthen the use of AOP network in the next-generation risk assessment of irradiation-related diseases.

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UVC和重离子辐射的转录组剂量反应揭示了免疫损伤的途径

辐照诱导的免疫损伤与人类免疫疾病有关，如骨髓增生异常综合征（MDS）和白血病。免疫细胞对基因组不稳定的全局分子反应可以通过转录组学来鉴定。然而，在以往的机制研究中，很难将分子机制与疾病结局联系起来。本研究通过鉴定差异表达基因（DEG）的基因表达模式，计算每个DEG的起点（POD）和分子通路，揭示了暴露于紫外线和重离子辐射下的人CD4+ T淋巴细胞的转录组剂量反应，为定量阐明辐照诱导免疫损伤的生物学过程提供了机会。通过将分子途径映射到生物事件级联中，确定了辐射相关白血病的两个潜在不良结局途径（AOPs），这为毒理学机制提供了表型锚定。此外，本研究还揭示了NOP14/ NOP14- as1可能是辐射诱导免疫损伤的潜在生物标志物。我们的工作加强了AOP网络在下一代辐射相关疾病风险评估中的应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology in Vitro 医学-毒理学

CiteScore

6.50

自引率

3.10%

发文量

181

审稿时长

65 days

期刊介绍： Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.