Format:
Online-Ressource
ISSN:
1521-4141
Content:
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.
In:
volume:35
In:
number:11
In:
year:2005
In:
pages:3364-3375
In:
extent:12
In:
European journal of immunology, Weinheim : Wiley-VCH, 1971-, 35, Heft 11 (2005), 3364-3375 (gesamt 12), 1521-4141
Language:
English
DOI:
10.1002/eji.200535192
URN:
urn:nbn:de:101:1-2023090805403821648663
URL:
https://doi.org/10.1002/eji.200535192
URL:
https://nbn-resolving.org/urn:nbn:de:101:1-2023090805403821648663
URL:
https://d-nb.info/130185378X/34
URL:
https://doi.org/10.1002/eji.200535192
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