Candéias Serge M, Mika Justyna, Finnon Paul, Verbiest Tom, Finnon Rosemary, Brown Natalie, Bouffler Simon, Polanska Joanna, Badie Christophe
CEA, Fundamental Research Division, Biosciences and Biotechnologies Institute, Laboratory of Chemistry and Biology of Metals, 38054, Grenoble, France.
Laboratory of Chemistry and Biology of Metals, CNRS, UMR5249, 38054, Grenoble, France.
Cell Mol Life Sci. 2017 Dec;74(23):4339-4351. doi: 10.1007/s00018-017-2581-2. Epub 2017 Jun 30.
While the biological effects of high-dose-ionizing radiation on human health are well characterized, the consequences of low-dose radiation exposure remain poorly defined, even though they are of major importance for radiological protection. Lymphocytes are very radiosensitive, and radiation-induced health effects may result from immune cell loss and/or immune system impairment. To decipher the mechanisms of effects of low doses, we analyzed the modulation of the T-cell receptor gene repertoire in mice exposed to a single low (0.1 Gy) or high (1 Gy) dose of radiation. High-throughput T-cell receptor gene profiling was used to visualize T-lymphocyte dynamics over time in control and irradiated mice. Radiation exposure induces "aging-like" effects on the T-cell receptor gene repertoire, detectable as early as 1 month post-exposure and for at least 6 months. Surprisingly, these effects are more pronounced in animals exposed to 0.1 Gy than to 1 Gy, where partial correction occurs over time. Importantly, we found that low-dose radiation effects are partially due to the hematopoietic stem cell impairment. Collectively, our findings show that acute low-dose radiation exposure specifically results in long-term alterations of the T-lymphocyte repertoire.
虽然高剂量电离辐射对人类健康的生物学影响已得到充分表征，但低剂量辐射暴露的后果仍不明确，尽管它们对放射防护至关重要。淋巴细胞对辐射非常敏感，辐射诱导的健康影响可能源于免疫细胞损失和/或免疫系统损伤。为了解析低剂量辐射的作用机制，我们分析了暴露于单次低剂量（0.1 Gy）或高剂量（1 Gy）辐射的小鼠中T细胞受体基因库的调节情况。利用高通量T细胞受体基因谱分析来观察对照小鼠和受辐照小鼠随时间的T淋巴细胞动态变化。辐射暴露对T细胞受体基因库产生“衰老样”影响，最早在暴露后1个月即可检测到，且至少持续6个月。令人惊讶的是，这些影响在暴露于0.1 Gy的动物中比在暴露于1 Gy的动物中更为明显，后者随时间会出现部分纠正。重要的是，我们发现低剂量辐射效应部分归因于造血干细胞损伤。总体而言，我们的研究结果表明，急性低剂量辐射暴露会特别导致T淋巴细胞库的长期改变。
