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High\u2010dose 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\u2010dose 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\u2010\u03b1. Furthermore, our investigation unveiled a marked increase in DNA\u2010damaged 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\u2010damaged 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\u2010\u03b1\u2010producing neutrophils, and due to the prevention of apoptosis induction, a lingering population of DNA\u2010damaged 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\u2010irradiated skin. These findings contribute to a deeper understanding of the intricate mechanisms underlying acute sunburn responses and their implications for UV\u2010induced skin cancer.<\/jats:p>","DOI":"10.1002\/eji.202451020","type":"journal-article","created":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T15:15:45Z","timestamp":1726586145000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Langerhans cells orchestrate apoptosis of DNA\u2010damaged keratinocytes upon high\u2010dose UVB skin exposure"],"prefix":"10.1002","volume":"54","author":[{"given":"Daniela","family":"Ortner","sequence":"first","affiliation":[{"name":"Department of Dermatology, Venereology &amp; Allergology Medical University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Strandt","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology &amp; Allergology Medical University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph H.","family":"Tripp","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology &amp; 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