Radiation- and Age-Associated Changes in Peripheral Blood Dendritic Cell Populations among Aging Atomic Bomb Survivors in Japan
Radiation- and Age-Associated Changes in Peripheral Blood Dendritic Cell Populations among Aging Atomic Bomb Survivors in Japan
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DOI：
10.1667/rr4854
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发表时间：
2018-01-01
影响因子：
3.4
通讯作者：
Kusunoki, Yoichiro
中科院分区：
文献类型：
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作者：
Kajimura, Junko;Lynch, Heather E.;Kusunoki, Yoichiro
以前对原子弹幸存者的免疫学研究表明，辐射暴露会导致长期的变化，类似于T细胞适应性免疫中观察到的免疫老化。然而，据我们所知，辐射对树突状细胞(DC)的晚期影响尚未在人类身上得到研究，树突状细胞是T细胞激活和分化的关键协调者。在目前的研究中，我们假设在229名日本原子弹幸存者中，循环中的常规DC(CDCs)和血浆细胞样DC(PDCs)的数量和功能将随着辐射剂量的增加而减少。总体而言，证据不支持这一假设，没有观察到DC的整体变化或随着辐射剂量而观察到的功能变化。对辐射剂量、年龄和性别影响的多变量回归分析表明，DC总数和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。体外对Toll样受体刺激后DC的基因表达谱进行的等级聚类分析发现，两组参与者在CDCs中与抗原提呈和细胞因子/趋化因子产生相关的基因的年龄相关表达水平不同。这些结果表明，随着年龄的增长，DC计数减少，基因簇的表达水平发生变化。在辐射暴露60多年后，我们也观察到与辐射相关的PDC计数的变化，但仅限于女性。(C)2018年，由辐射研究学会提供
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. (C) 2018 by Radiation Research Society