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dc.contributor.author
Berndt, Nicole
dc.contributor.author
Wolf, Christine
dc.contributor.author
Fischer, Kristina
dc.contributor.author
Cura Costa, Emanuel
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dc.contributor.author
Knuschke, Peter
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Zimmermann, Nick
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Schmidt, Franziska
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Merkel, Martin
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Chara, Osvaldo
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dc.contributor.author
Lee Kirsch, Min Ae
dc.contributor.author
Günther, Claudia
dc.date.available
2023-09-22T13:22:18Z
dc.date.issued
2022-03
dc.identifier.citation
Berndt, Nicole; Wolf, Christine; Fischer, Kristina; Cura Costa, Emanuel; Knuschke, Peter; et al.; Photosensitivity and cGAS-Dependent IFN-1 Activation in Patients with Lupus and TREX1 Deficiency; Nature Publishing Group; Journal Of Investigative Dermatology; 142; 3; 3-2022; 633-640.e6
dc.identifier.issn
0022-202X
dc.identifier.uri
http://hdl.handle.net/11336/212668
dc.description.abstract
The exonuclease TREX1 safeguards the cells against DNA accumulation in the cytosol and thereby prevents innate immune activation and autoimmunity. TREX1 mutations lead to chronic DNA damage and cell-intrinsic IFN-1 response. Associated disease phenotypes include Aicardi‒Goutières syndrome, familial chilblain lupus, and systemic lupus erythematosus. Given the role of UV light in lupus pathogenesis, we assessed sensitivity to UV light in patients with lupus and TREX1 mutation by phototesting, which revealed enhanced photosensitivity. TREX1-deficient fibroblasts and keratinocytes generated increased levels of ROS in response to UV irradiation as well as increased levels of 8-oxo-guanine lesions after oxidative stress. Likewise, the primary UV-induced DNA lesions cyclobutane pyrimidine dimers were induced more strongly in TREX1-deficient cells. Further analysis revealed that single-stranded DNA regions, frequently formed during DNA replication and repair, promote cyclobutane pyrimidine dimer formation. Together, this resulted in a strong UV-induced DNA damage response that was associated with a cGAS-dependent IFN-1 activation. In conclusion, these findings link chronic DNA damage to photosensitivity and IFN-1 production in TREX1 deficiency and explain the induction of disease flares on UV exposure in patients with lupus and TREX1 mutation.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Nature Publishing Group
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dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
INTERFERON STIMULATED GENES
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CUTANEOUS LUPUS
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UV IRRADIATION
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PYRIMIDINE DIMERS
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Otras Medicina Básica
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dc.subject.classification
Medicina Básica
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dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
Photosensitivity and cGAS-Dependent IFN-1 Activation in Patients with Lupus and TREX1 Deficiency
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2023-06-29T10:27:27Z
dc.journal.volume
142
dc.journal.number
3
dc.journal.pagination
633-640.e6
dc.journal.pais
Reino Unido
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dc.journal.ciudad
Londres
dc.description.fil
Fil: Berndt, Nicole. Universitätsklinikum Carl Gustav Carus; Alemania
dc.description.fil
Fil: Wolf, Christine. Universitätsklinikum Carl Gustav Carus; Alemania
dc.description.fil
Fil: Fischer, Kristina. Universitätsklinikum Carl Gustav Carus; Alemania
dc.description.fil
Fil: Cura Costa, Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; Argentina
dc.description.fil
Fil: Knuschke, Peter. Universitätsklinikum Carl Gustav Carus; Alemania
dc.description.fil
Fil: Zimmermann, Nick. Universitätsklinikum Carl Gustav Carus; Alemania
dc.description.fil
Fil: Schmidt, Franziska. Universitätsklinikum Carl Gustav Carus; Alemania
dc.description.fil
Fil: Merkel, Martin. Universitätsklinikum Carl Gustav Carus; Alemania
dc.description.fil
Fil: Chara, Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Technische Universität Dresden; Alemania
dc.description.fil
Fil: Lee Kirsch, Min Ae. Universitätsklinikum Carl Gustav Carus; Alemania
dc.description.fil
Fil: Günther, Claudia. Universitätsklinikum Carl Gustav Carus; Alemania
dc.journal.title
Journal Of Investigative Dermatology
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.jid.2021.04.037
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0022202X21016869
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