First Author | Ma L | Year | 2005 |
Journal | Eur J Immunol | Volume | 35 |
Issue | 11 | Pages | 3364-75 |
PubMed ID | 16224814 | Mgi Jnum | J:113764 |
Mgi Id | MGI:3687623 | Doi | 10.1002/eji.200535192 |
Citation | Ma L, et al. (2005) Systemic autoimmune disease induced by dendritic cells that have captured necrotic but not apoptotic cells in susceptible mouse strains. Eur J Immunol 35(11):3364-75 |
abstractText | 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. |