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

J Invest Dermatol. 2020 Aug;140(8):1589-1598.e3. doi: 10.1016/j.jid.2019.09.029. Epub 2020 Jan 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alarmins / metabolism
  • Cells, Cultured
  • Chemokine CXCL10 / metabolism
  • DNA / metabolism*
  • Herpes Simplex / immunology*
  • Herpes Simplex / virology
  • Herpesvirus 1, Human / immunology
  • Host Microbial Interactions / immunology
  • Humans
  • Immunity, Innate*
  • Keratinocytes / immunology*
  • Keratinocytes / metabolism
  • Primary Cell Culture
  • Ribonucleases / metabolism*


  • Alarmins
  • CXCL10 protein, human
  • Chemokine CXCL10
  • DNA
  • Ribonucleases
  • Ribonuclease 7