Title: Intrinsic interferon signature in myeloid dendritic cells from lupus-prone mice precedes disease onset (47.1)
Abstract: Abstract Systemic Lupus Erythematosus (SLE) patients over-express Type I Interferon (IFN) responsive genes but the cellular source of this IFN Signature is unclear. We found that ex vivo dendritic cells (DCs) from Sle1,2,3 lupus-prone mice express the IFN Signature. To test if the IFN Signature was intrinsic to DCs, we grew myeloid DCs in vitro from bone marrow in GM-CSF medium (BMDCs), and found that IFN responsive genes, analyzed by real-time RT-PCR, are constitutively over-expressed in Sle1,2,3 BMDCs as compared to non-autoimmune C57BL/6 BMDCs: expression of IFN-b, signaling molecules IRF-7, STAT1 and STAT2, and IFN responsive genes ISG-15, IL-15, Oas-3 and Mx1, was significantly higher in lupus BMDCs than in C57BL/6 BMDCs in absence of any stimulation. The IFN Signature was similar in BMDCs from mice negative for autoAbs and from mice with high autoAb titers, suggesting that the IFN Signature precedes disease onset and is not affected by the autoimmune process. Sle1,2,3 BMDCs were hyper-sensitive to nucleic acids CpGs and R848, confirming a role for TLR7 and TLR9 in lupus pathogenesis. However, treatment with oligonucleotide sequences inhibitory for TLR7/TLR9 did not suppress the constitutive over-expression of IFN responsive genes, indicating that DC IFN Signature is independent from chronic exposure to TLR7/9 ligands. We suggest that myeloid DCs are a source of IFN Signature in Sle1,2,3 mice and have an intrinsic dysregulation in the IFN signaling/response.
Publication Year: 2011
Publication Date: 2011-04-01
Language: en
Type: article
Indexed In: ['crossref']
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