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首页> 外文期刊>Nature immunology >CDKN1A regulates Langerhans cell survival and promotes T-reg cell generation upon exposure to ionizing irradiation
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CDKN1A regulates Langerhans cell survival and promotes T-reg cell generation upon exposure to ionizing irradiation

机译:暴露于电离辐射下,CDKN1A调节朗格汉斯细胞存活并促进T-reg细胞生成

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Treatment with ionizing radiation (IR) can lead to the accumulation of tumor-infiltrating regulatory T cells (T-reg cells) and subsequent resistance of tumors to radiotherapy. Here we focused on the contribution of the epidermal mononuclear phagocytes Langerhans cells (LCs) to this phenomenon because of their ability to resist depletion by high-dose IR. We found that LCs resisted apoptosis and rapidly repaired DNA damage after exposure to IR. In particular, we found that the cyclin-dependent kinase inhibitor CDKN1A (p21) was overexpressed in LCs and that Cdkn1a(-/-) LCs underwent apoptosis and accumulated DNA damage following IR treatment. Wild-type LCs upregulated major histocompatibility complex class II molecules, migrated to the draining lymph nodes and induced an increase in T-reg cell numbers upon exposure to IR, but Cdkn1a(-/-) LCs did not. Our findings suggest a means for manipulating the resistance of LCs to IR to enhance the response of cutaneous tumors to radiotherapy.
机译:电离辐射(IR)的治疗可导致肿瘤浸润性调节性T细胞(T-reg细胞)的积累和随后的肿瘤对放射疗法的抵抗力。在这里,我们将重点放在表皮单核吞噬细胞Langerhans细胞(LC)对这种现象的贡献上,因为它们具有抵抗高剂量IR消耗的能力。我们发现LC暴露于IR后可抵抗凋亡并迅速修复DNA损伤。特别是,我们发现细胞周期蛋白依赖性激酶抑制剂CDKN1A(p21)在LC中过表达,而Cdkn1a(-/-)LC在IR处理后发生凋亡并累积了DNA损伤。野生型LCs上调主要的组织相容性复杂的II类分子,迁移到引流淋巴结,并在暴露于IR后诱导T-reg细胞数增加,但Cdkn1a(-/-)LCs没有。我们的发现提出了一种手段,可以控制LC对IR的抵抗力,从而增强皮肤肿瘤对放射疗法的反应。

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