a Department of Molecular Biosciences.
b Duke Regional Biocontainment Laboratory, Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina.
Radiat Res. 2018 Jan;189(1):84-94. doi: 10.1667/RR4854.
Previous immunological studies in atomic bomb survivors have suggested that radiation exposure leads to long-lasting changes, similar to immunological aging observed in T-cell-adaptive immunity. However, to our knowledge, late effects of radiation on dendritic cells (DCs), the key coordinators for activation and differentiation of T cells, have not yet been investigated in humans. In the current study, we hypothesized that numerical and functional decreases would be observed in relationship to radiation dose in circulating conventional DCs (cDCs) and plasmacytoid DCs (pDCs) among 229 Japanese A-bomb survivors. Overall, the evidence did not support this hypothesis, with no overall changes in DCs or functional changes observed with radiation dose. Multivariable regression analysis for radiation dose, age and gender effects revealed that total DC counts as well as subpopulation counts decreased in relationship to increasing age. Further analyses revealed that in women, absolute numbers of pDCs showed significant decreases with radiation dose. A hierarchical clustering analysis of gene expression profiles in DCs after Toll-like receptor stimulation in vitro identified two clusters of participants that differed in age-associated expression levels of genes involved in antigen presentation and cytokine/chemokine production in cDCs. These results suggest that DC counts decrease and expression levels of gene clusters change with age. More than 60 years after radiation exposure, we also observed changes in pDC counts associated with radiation, but only among women.
先前在原子弹幸存者中的免疫学研究表明，辐射暴露会导致类似于 T 细胞适应性免疫中观察到的免疫衰老的持久变化。然而，据我们所知，人类尚未研究过辐射对树突状细胞 (DC) 的晚期影响，DC 是 T 细胞激活和分化的关键协调者。在当前的研究中，我们假设在 229 名日本原子弹幸存者中，循环常规树突状细胞 (cDC) 和浆细胞样树突状细胞 (pDC) 中，与辐射剂量相关的数值和功能下降将会观察到。总的来说，没有证据支持这一假设，没有观察到 DC 或功能变化与辐射剂量有关。对辐射剂量、年龄和性别效应的多变量回归分析表明，总 DC 计数以及亚群计数随着年龄的增加而减少。进一步的分析表明，在女性中，pDC 的绝对数量随着辐射剂量的增加而显著减少。体外 Toll 样受体刺激后 DC 基因表达谱的层次聚类分析确定了两个参与者聚类，它们在 cDC 中参与抗原呈递和细胞因子/趋化因子产生的基因的年龄相关表达水平上存在差异。这些结果表明，DC 计数减少，与年龄相关的基因簇表达水平发生变化。在辐射暴露 60 多年后，我们还观察到与辐射相关的 pDC 计数的变化，但仅在女性中。
