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

Apoptosis Langerhans cells Neutrophils Skin inflammation UVB‐induced sunburn

Journal

European journal of immunology
ISSN: 1521-4141
Titre abrégé: Eur J Immunol
Pays: Germany
ID NLM: 1273201

Informations de publication

Date de publication:
17 Sep 2024
Historique:
revised: 27 08 2024
received: 19 01 2024
accepted: 30 08 2024
medline: 17 9 2024
pubmed: 17 9 2024
entrez: 17 9 2024
Statut: aheadofprint

Résumé

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.

Identifiants

pubmed: 39288297
doi: 10.1002/eji.202451020
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2451020

Subventions

Organisme : Austrian Science Fund
ID : 10.55776/T737
Organisme : Austrian Science Fund
ID : 10.55776/P27001
Organisme : Austrian Science Fund
ID : 10.55776/P21487
Organisme : Austrian Science Fund
ID : 10.55776/P33855
Organisme : Austrian Science Fund
ID : 10.55776/DOC82
Organisme : Marie Sklodowska-Curie
ID : 641549/Immutrain
Organisme : Austrian Academy of Sciences
ID : DOC/26015

Informations de copyright

© 2024 The Author(s). European Journal of Immunology published by Wiley‐VCH GmbH.

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Auteurs

Daniela Ortner (D)

Department of Dermatology, Venereology & Allergology, Medical University of Innsbruck, Innsbruck, Austria.

Helen Strandt (H)

Department of Dermatology, Venereology & Allergology, Medical University of Innsbruck, Innsbruck, Austria.

Christoph H Tripp (CH)

Department of Dermatology, Venereology & Allergology, Medical University of Innsbruck, Innsbruck, Austria.

Sarah Spoeck (S)

Division of Developmental Immunology, Medical University of Innsbruck, Innsbruck, Austria.

Athanasios Seretis (A)

Research Institute for Biomedical Ageing Research, University of Innsbruck, Innsbruck, Austria.

Florian Hornsteiner (F)

Department of Dermatology, Venereology & Allergology, Medical University of Innsbruck, Innsbruck, Austria.

Sophie Dieckmann (S)

Department of Dermatology, Venereology & Allergology, Medical University of Innsbruck, Innsbruck, Austria.

Matthias Schmuth (M)

Department of Dermatology, Venereology & Allergology, Medical University of Innsbruck, Innsbruck, Austria.

Patrizia Stoitzner (P)

Department of Dermatology, Venereology & Allergology, Medical University of Innsbruck, Innsbruck, Austria.

Classifications MeSH