Increased reactivity of dendritic cells from aged subjects to self-antigen, the human DNA.
Increased reactivity of dendritic cells from aged subjects to self-antigen, the human DNA.
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DOI：
10.4049/jimmunol.182.2.1138
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发表时间：
2009-01-15
影响因子：
4.4
通讯作者：
Gupta, Sudhir
中科院分区：
文献类型：
--
作者：
Agrawal, Anshu;Tay, Aa;Ton, Steven;Agrawal, Sudhanshu;Gupta, Sudhir
免疫功能减弱和慢性炎症是衰老的标志。其根本原因尚不清楚。在这项研究中，我们发现老年受试者的树突状细胞对自身抗原的反应性增强，这是导致年龄相关性炎症的潜在机制之一。与此一致，老年受试者的DC与年轻受试者的DC相比，通过分泌更多的I型干扰素和白介素6，对细胞内人类DNA(一种自身抗原)表现出更高的反应性。此外，伴随着共刺激分子CD80和CD86的上调。与年轻受试者相比，这些来自老年受试者的DNA诱导的DC促进了T细胞的增殖，进一步证实了我们的发现。对信号机制的研究表明，与年轻受试者相比，来自老年受试者的DNA刺激的DC显示出显著更高水平的干扰素调节因子-3和核因子-kappaB活性。更重要的是，老年受试者的DC在基础水平上表现出更高水平的核因子-kappaB激活，表明激活状态增强。DC的这种激活状态可能是其对自身抗原(如DNA)反应性增强的原因，这反过来又导致了与年龄相关的慢性炎症。
Diminished immune functions and chronic inflammation are hallmarks of aging. The underlying causes are not well understood. In this investigation, we show an increased reactivity of dendritic cells from aged subjects to self-antigens as one of the potential mechanism contributing to age-associated inflammation. Consistent with this, DCs from aged subjects display increased reactivity to intracellular human DNA, a self-antigen, by secreting enhanced quantities of type I interferon and Interleukin-6 compared to the DCs from young subjects. Furthermore, this is accompanied by an increased upregulation of costimulatory molecules CD80 and CD86. These DNA primed DCs from aged subjects enhanced T cell proliferation compared to the young subjects further substantiating our findings. Investigations of signaling mechanisms revealed that DNA-stimulated DCs from aged subjects displayed a significantly higher level of interferon regulatory factor-3 and NF-kappaB activity compared to their young counterparts. More importantly, DCs from aged subjects displayed a higher level of NF-kappaB activation at the basal level suggesting an increased state of activation. This activated state of DCs may be responsible for their increased reactivity to self-antigens such as DNA, which in turn contributes to the age-associated chronic inflammation.
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DOI：
10.1084/jem.20051654
发表时间：
2005-11-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Okabe Y;Kawane K;Akira S;Taniguchi T;Nagata S
通讯作者：
Nagata S
影响因子：
30.8
作者：
Napirei, M;Karsunky, H;Möröy, T
通讯作者：
Möröy, T
影响因子：
16.8
作者：
Fukao, T;Koyasu, S
通讯作者：
Koyasu, S
影响因子：
13.6
作者：
Boren, E;Gershwin, ME
通讯作者：
Gershwin, ME
影响因子：
4.6
作者：
Aprahamian, T.;Takemura, Y.;Walsh, K.
通讯作者：
Walsh, K.