Systemic autoimmune disease induced by dendritic cells that have captured necrotic but not apoptotic cells in susceptible mouse strains

Eur J Immunol. 2005 Nov;35(11):3364-75. doi: 10.1002/eji.200535192.


Systemic lupus erythematosus (SLE) is an autoimmune disorder of a largely unknown etiology. Anti-double-stranded (ds) DNA antibodies are a classic hallmark of the disease, although the mechanism underlying their induction remains unclear. We demonstrate here that, in both lupus-prone and normal mouse strains, strong anti-dsDNA antibody responses can be induced by dendritic cells (DC) that have ingested syngeneic necrotic (DC/nec), but not apoptotic (DC/apo), cells. Clinical manifestations of lupus were evident, however, only in susceptible mouse strains, which correlate with the ability of DC/nec to release IFN-gamma and to induce the pathogenic IgG2a anti-dsDNA antibodies. Injection of DC/nec not only accelerated disease progression in the MRL/MpJ-lpr/lpr lupus-prone mice but also induced a lupus-like disease in the MRL/MpJ-+/+ wild-type control strain. Immune complex deposition was readily detectable in the kidneys, and the mice developed proteinuria. Strikingly, female MRL/MpJ-+/+ mice that had received DC/nec, but not DC/apo, developed a 'butterfly' facial lesion resembling a cardinal feature of human SLE. Our study therefore demonstrates that DC/nec inducing a Th1 type of responses, which are otherwise tightly regulated in a normal immune system, may play a pivotal role in SLE pathogenesis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Antinuclear / biosynthesis
  • Apoptosis / immunology*
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / pathology
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • DNA / immunology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology
  • Disease Susceptibility / immunology
  • Erythema / immunology
  • Erythema / pathology
  • Face
  • Female
  • Humans
  • Kidney / immunology
  • Kidney / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred MRL lpr
  • Necrosis
  • Proteinuria / immunology
  • Proteinuria / pathology
  • Skin Ulcer / immunology
  • Skin Ulcer / pathology


  • Antibodies, Antinuclear
  • Cytokines
  • DNA