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J Invest Dermatol. 2020 Jan 21. pii: S0022-202X(20)30039-7. doi: 10.1016/j.jid.2019.09.029. [Epub ahead of print]

RNase 7 Promotes Sensing of Self-DNA by Human Keratinocytes and Activates an Antiviral Immune Response.

Author information

1
Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany; Hannover Unified Biobank, Hannover Medical School, Germany. Electronic address: Kopfnagel.Verena@mh-hannover.de.
2
Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
3
Department of Dermatology, University Hospital Schleswig-Holstein, Kiel Campus, Kiel, Germany.
4
PLANTON GmbH, Am Kiel Kanal, Kiel, Germany.
5
Institute of Virology, Hannover Medical School, Hannover, Germany.
6
Institute of Virology, Hannover Medical School, Hannover, Germany; German Center of Infection Research (DZIF), Hannover, Germany.
7
Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany.

Abstract

RNase 7 is one of the major antimicrobial peptides (AMPs) secreted by keratinocytes. The AMPs human beta defensin 2 and LL-37 promote the toll-like receptor 9-mediated activation of human plasmacytoid dendritic cells (pDCs) by human self-DNA; however, whether keratinocytes respond in a similar way has not yet been addressed. Keratinocytes express several receptors for the detection of cytosolic DNA. Here, we investigated the activation of keratinocytes by RNase 7 in combination with human DNA. The stimulation of keratinocytes with RNase 7 and human DNA induced a strong increase in the production of IP-10. Of note, the stimulation of keratinocytes with human beta defensin 2 and LL-37 in combination with DNA failed to induce the production of IP-10. The production of IP-10 was mediated by the induction of the type I interferon IFN-β and was significantly downregulated by blocking of the interferon-α/β receptor and inhibition of stimulator of IFN genes. In addition, the pretreatment of keratinocytes with RNase 7 and DNA significantly reduced the herpes simplex virus-1 infection of human keratinocytes. This study demonstrates that RNase 7 functions as an alarmin by converting self-DNA into a danger signal that directly activates an antiviral immune response in human keratinocytes without the involvement of plasmacytoid dendritic cells.

PMID:
31978413
DOI:
10.1016/j.jid.2019.09.029

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