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Start Over Author "Zimmermann, N" Journal journal of investigative dermatology
6 results on '"Zimmermann, N"'

4. Photosensitivity and cGAS-Dependent IFN-1 Activation in Patients with Lupus and TREX1 Deficiency.

Author

Berndt N, Wolf C, Fischer K, Cura Costa E, Knuschke P, Zimmermann N, Schmidt F, Merkel M, Chara O, Lee-Kirsch MA, and Günther C

Subjects
DNA genetics, Exodeoxyribonucleases genetics, Humans, Nucleotidyltransferases genetics, Phosphoproteins genetics, Autoimmune Diseases of the Nervous System genetics, Autoimmune Diseases of the Nervous System pathology, Chilblains genetics, Lupus Erythematosus, Cutaneous genetics
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., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2022
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5. SMARCAD1 Haploinsufficiency Underlies Huriez Syndrome and Associated Skin Cancer Susceptibility.

Author

Günther C, Lee-Kirsch MA, Eckhard J, Matanovic A, Kerscher T, Rüschendorf F, Klein B, Berndt N, Zimmermann N, Flachmeier C, Thuß T, Lucas N, Marenholz I, Esparza-Gordillo J, Hübner N, Traupe H, Delaporte E, and Lee YA

Subjects
Adult, Carcinoma, Squamous Cell pathology, Cells, Cultured, Female, Fibroblasts, Haploinsufficiency, Humans, Isoenzymes genetics, Keratinocytes, Keratosis pathology, Male, Middle Aged, Pedigree, Polymorphism, Single Nucleotide, Primary Cell Culture, Scleroderma, Localized pathology, Skin cytology, Skin pathology, Skin Neoplasms pathology, Whole Genome Sequencing, Young Adult, Carcinoma, Squamous Cell genetics, DNA Helicases genetics, Genetic Predisposition to Disease, Keratosis genetics, Scleroderma, Localized genetics, Skin Neoplasms genetics
Published
2018
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6. Deregulated type I IFN response in TREX1-associated familial chilblain lupus.

Author

Peschke K, Friebe F, Zimmermann N, Wahlicht T, Schumann T, Achleitner M, Berndt N, Luksch H, Behrendt R, Lee-Kirsch MA, Roers A, and Günther C

Subjects
Animals, Autoimmunity immunology, Chilblains immunology, Chilblains metabolism, Child, Exodeoxyribonucleases immunology, Exodeoxyribonucleases metabolism, Heterozygote, Humans, Interferon Type I immunology, Lupus Erythematosus, Cutaneous immunology, Lupus Erythematosus, Cutaneous metabolism, Mice, Mice, Knockout, Phosphoproteins immunology, Phosphoproteins metabolism, Autoimmunity genetics, Chilblains genetics, Exodeoxyribonucleases genetics, Interferon Type I metabolism, Lupus Erythematosus, Cutaneous genetics, Phosphoproteins genetics
Published
2014
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