Systemic autoimmune disease induced by dendritic cells that have captured necrotic but not apoptotic cells in susceptible mouse strains - PubMed (original) (raw)

Comparative Study

. 2005 Nov;35(11):3364-75.

doi: 10.1002/eji.200535192.

Kwok-Wah Chan, Nigel J Trendell-Smith, Adrian Wu, Lina Tian, Audrey C Lam, Albert K Chan, Chi-Kin Lo, Stanley Chik, King-Hung Ko, Christina K W To, Siu-Kee Kam, Xiao-Song Li, Cui-Hong Yang, Suet Yi Leung, Mun-Hon Ng, David I Stott, G Gordon MacPherson, Fang-Ping Huang

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Comparative Study

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

Liang Ma et al. Eur J Immunol. 2005 Nov.

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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-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.

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