朗格汉斯细胞在高剂量紫外线照射皮肤时协调 DNA 损坏的角质细胞凋亡

IF 4.5 3区 医学 Q2 IMMUNOLOGY
Daniela Ortner, Helen Strandt, Christoph H. Tripp, Sarah Spoeck, Athanasios Seretis, Florian Hornsteiner, Sophie Dieckmann, Matthias Schmuth, Patrizia Stoitzner
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引用次数: 0

摘要

紫外线(UV)照射皮肤会导致突变,从而诱发黑色素瘤和非黑色素瘤皮肤癌。高剂量的紫外线照射会引发以炎症为特征的剧烈皮肤反应,导致急性晒伤。这种反应包括形成晒伤细胞和角质细胞(KC),当 DNA 损伤修复机制不足时,角质细胞会发生程序性细胞死亡(凋亡)。本研究的主要目的是阐明朗格汉斯细胞(LC)在强烈紫外线照射皮肤后参与急性晒伤的发生。为此,我们对小鼠的背侧皮肤进行了一次高剂量的 UVB 照射,并分析了皮肤组织内发生的即时免疫反应。急性晒伤触发了 LC 的激活,同时中性粒细胞迅速涌入,产生 TNF-α。此外,我们的研究还发现,DNA受损的 KC 显著增加,随后诱导了这些细胞的凋亡。重要的是,我们证明了炎症级联、DNA 损伤的 KC 细胞凋亡的启动和皮肤中 LC 的存在之间的重要联系。在暴露于紫外线后,我们观察到 LC 可调节皮肤中的趋化因子反应,从而影响中性粒细胞的迁移。缺乏 LC 的皮肤显示炎症减轻,产生 TNF-α 的中性粒细胞减少,而且由于凋亡诱导被阻止,DNA 受损的 KC 群体持续存在,可能会带来基因组持久改变的风险。总之,我们的研究结果强调了 LC 在维持 UVB 照射下皮肤的稳态中的关键作用。这些发现有助于深入了解急性晒伤反应的复杂机制及其对紫外线诱发皮肤癌的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Langerhans cells orchestrate apoptosis of DNA-damaged keratinocytes upon high-dose UVB skin exposure

Langerhans cells orchestrate apoptosis of DNA-damaged keratinocytes upon high-dose UVB skin exposure

Ultraviolet (UV) irradiation of the skin causes mutations that can promote the development of melanoma and nonmelanoma skin cancer. High-dose UVB exposure triggers a vigorous skin reaction characterized by inflammation resulting in acute sunburn. This response includes the formation of sunburn cells and keratinocytes (KC) undergoing programmed cell death (apoptosis) when repair mechanisms of DNA damage are inadequate. The primary objective of this research was to clarify the involvement of Langerhans cells (LC) in the development of acute sunburn following intense UVB skin irradiation. To address this, we subjected the dorsal skin of mice to a single high-dose UVB exposure and analyzed the immediate immune response occurring within the skin tissue. Acute sunburn triggered an activation of LC, coinciding with a rapid influx of neutrophils that produced TNF-α. Furthermore, our investigation unveiled a marked increase in DNA-damaged KC and the subsequent induction of apoptosis in these cells. Importantly, we demonstrate a crucial link between the inflammatory cascade, the initiation of apoptosis in DNA-damaged KC, and the presence of LC in the skin. LC were observed to modulate the chemokine response in the skin following exposure to UVB, thereby affecting the trafficking of neutrophils. Skin lacking LC revealed diminished inflammation, contained fewer TNF-α-producing neutrophils, and due to the prevention of apoptosis induction, a lingering population of DNA-damaged KC, presumably carrying the risk of enduring genomic alterations. In summary, our results underscore the pivotal role of LC in preserving the homeostasis of UVB-irradiated skin. These findings contribute to a deeper understanding of the intricate mechanisms underlying acute sunburn responses and their implications for UV-induced skin cancer.

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来源期刊
CiteScore
8.30
自引率
3.70%
发文量
224
审稿时长
2 months
期刊介绍: The European Journal of Immunology (EJI) is an official journal of EFIS. Established in 1971, EJI continues to serve the needs of the global immunology community covering basic, translational and clinical research, ranging from adaptive and innate immunity through to vaccines and immunotherapy, cancer, autoimmunity, allergy and more. Mechanistic insights and thought-provoking immunological findings are of interest, as are studies using the latest omics technologies. We offer fast track review for competitive situations, including recently scooped papers, format free submission, transparent and fair peer review and more as detailed in our policies.
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