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- Title
Systemic autoimmune disease induced by dendritic cells that have captured necrotic but not apoptotic cells in susceptible mouse strains.
- Authors
Ma, Liang; Chan, Kwok-Wah; Trendell-Smith, Nigel J.; Wu, Adrian; Tian, Lina; Lam, Audrey C.; Chan, Albert K.; Lo, Chi-Kin; Chik, Stanley; Ko, King-Hung; To, Christina K. W.; Kam, Siu-Kee; Li, Xiao-Song; Yang, Cui-Hong; Leung, Suet Yi; Ng, Mun-Hon; Stott, David I.; MacPherson, G. Gordon; Huang, Fang-Ping
- Abstract
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-γ 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
European Journal of Immunology, 2005, Vol 35, Issue 11, p3364
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.200535192