Daniela Ortner, Helen Strandt, Christoph H. Tripp, Sarah Spoeck, Athanasios Seretis, Florian Hornsteiner, Sophie Dieckmann, Matthias Schmuth, Patrizia Stoitzner
{"title":"Langerhans cells orchestrate apoptosis of DNA-damaged keratinocytes upon high-dose UVB skin exposure","authors":"Daniela Ortner, Helen Strandt, Christoph H. Tripp, Sarah Spoeck, Athanasios Seretis, Florian Hornsteiner, Sophie Dieckmann, Matthias Schmuth, Patrizia Stoitzner","doi":"10.1002/eji.202451020","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 12","pages":""},"PeriodicalIF":4.5000,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451020","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Immunology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/eji.202451020","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
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.