Systemic autoimmune disease induced by dendritic cells that have captured necrotic but not apoptotic cells in susceptible mouse strains
Systemic autoimmune disease induced by dendritic cells that have captured necrotic but not apoptotic cells in susceptible mouse strains
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DOI：
10.1002/eji.200535192
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发表时间：
2005-11-01
影响因子：
5.4
通讯作者：
Huang, FP
中科院分区：
文献类型：
--
作者：
Ma, L;Chan, KW;Huang, FP
系统性红斑狼疮（SLE）是一种病因不明的自身免疫性疾病。抗双链（ds）DNA抗体是该疾病的典型标志，尽管其诱导的机制仍不清楚。我们在这里证明，在狼疮倾向和正常小鼠品系，强烈的抗dsDNA抗体反应可以诱导树突状细胞（DC），已摄入同系坏死（DC/NEC），但不凋亡（DC/载脂蛋白），细胞。狼疮的临床表现是明显的，然而，仅在易感小鼠品系，这与DC/nec释放IFN-γ和诱导致病性IgG 2a抗dsDNA抗体的能力。注射DC/nec不仅加速了MRL/MpJ-lpr/lpr狼疮易感小鼠的疾病进展，而且在MRL/MpJ-+/+野生型对照品系中诱导了狼疮样疾病。免疫复合物沉积在肾脏中很容易检测到，小鼠出现蛋白尿。引人注目的是，接受DC/nec而不是DC/apo的雌性MRL/MpJ-+/+小鼠出现了类似于人类SLE的主要特征的“蝴蝶”面部病变。因此，我们的研究表明，DC/nec诱导的Th 1型的反应，否则在正常的免疫系统中受到严格的调节，可能在SLE发病机制中发挥关键作用。
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.