Article Text

Download PDFPDF

PS5:92 Clarification of the role of dnase 1 on the onset of systemic lupus erythematosus in a murine model
  1. E Kenny1,
  2. U Abu Abed2,
  3. A Kuehl3,
  4. B Raupach1,
  5. V Brinkmann2 and
  6. A Zychlinsky1
  1. 1Max-Planck-Institute for infection biology, dept. of Cellular Microbiology, Berlin, Germany
  2. 2Max-Planck-Institute for infection biology, Microscopy Core Facility, Berlin, Germany
  3. 3Charite Universitaetsmedizin Berlin Forschungszentrum Immunwissenschaft RCIS, Berlin, Germany


Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease resulting in multi-organ damage and a high rate of morbidity. Onset of SLE is characterised by dysregulated activation of T and B lymphocytes and the production of autoantibodies directed against nuclear components. The autoantibodies generated during the onset of SLE often recognise components released by neutrophils during NETosis, a type of cell death defined by the generation of neutrophil extracellular traps (NETs). The endonuclease DNase1 has been shown to be involved in the clearance of NET components. The sera of SLE patients contain inhibitors of DNase 1 and/or anti-NET antibodies that block the ability of DNase 1 to degrade NETs. Thus, whilst NETs are important for clearing infection they must be tightly regulated and degraded to prevent the onset of autoimmunity.

In this study we monitored the production of auto-antibodies in the serum of wild type and DNase 1-deficient mice from the age of 2 to 12 months, along with proteinuria levels and the development of glomerulonephritis. We show that DNase 1-deficient mice develop a SLE-like phenotype with elevated auto-antibody production and kidney damage by 12 months. This model also demonstrates the female bias in SLE as the female DNase 1-defieicnt mice had the highest level of kidney damage. As DNase I activity, B cells and aberrant NETosis are central to progression of SLE understanding their mechanisms of action are of great therapeutic interest.

  • DNase 1
  • Neutrophil
  • Onset of Autoimmunity

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.