Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Epidermal Nbn deletion causes premature hair loss and a phenotype resembling psoriasiform dermatitis

Philipp Seidel, Martina Remus, Michael Delacher, Paulius Grigaravicius, David E. Reuss, Lucien Frappart, Andreas von Deimling, Markus Feuerer, Amir Abdollahi and Pierre-Olivier Frappart _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2016; 7:23006-23018. https://doi.org/10.18632/oncotarget.8470

Metrics: PDF 631 views  |   HTML 1140 views  |   ?  


Abstract

Philipp Seidel1,2, Martina Remus3, Michael Delacher4, Paulius Grigaravicius3, David E. Reuss5, Lucien Frappart6, Andreas von Deimling3,5, Markus Feuerer4, Amir Abdollahi1,2 and Pierre-Olivier Frappart3

1 Molecular and Translational Radiation Oncology, National Center for Tumor Diseases (NCT), Heidelberg University Medical School (HUMS), Heidelberg, Germany

2 German Cancer Consortium (DKTK) and Heidelberg Institute of Radiation Oncology (HIRO), German Cancer Research Center (DKFZ), Heidelberg, Germany

3 Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

4 Helmholtz Young Investigator Group Immune Tolerance, Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany

5 Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany

6 Leibniz Institute for Age Research - Fritz Lipmann Institute (FLI), Jena, Germany

Correspondence to:

Pierre-Olivier Frappart, email:

Keywords: inflammation, Nbn, psoriasiform dermatitis, skin, Gerotarget

Received: February 17, 2016 Accepted: March 22, 2016 Published: March 30, 2016

Abstract

Nijmegen Breakage Syndrome is a disease caused by NBN mutations. Here, we report a novel function of Nbn in skin homeostasis. We found that Nbn deficiency in hair follicle (HF) progenitors promoted increased DNA damage signaling, stimulating p16Ink4a up-regulation, Trp53 stabilization and cytokines secretion leading to HF-growth arrest and hair loss. At later stages, the basal keratinocytes layer exhibited also enhanced DNA damage response but in contrast to the one in HF progenitor was not associated with pro-inflammatory cytokines expression, but rather increased proliferation, lack of differentiation and immune response resembling psoriasiform dermatitis. Simultaneous Nbn and Trp53 inactivation significantly exacerbated this phenotype, due to the lack of inhibition of pro-inflammatory cytokines secretion by Trp53. Altogether, we demonstrated novel functions of Nbn in HF maintenance and prevention of skin inflammation and we provide a mechanistic explanation that links cell intrinsic DNA maintenance with large scale morphological tissue alterations.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 8470