Recently, we found that reduced expression of Fli-1 protein had a profound effect on disease development in the NZM2410 mice that are a strain derived by intercrossing NZW × NZB F1 mice. Fli-1+/− NZM2410 mice, like Fli-1+/− MRL/lpr mice, had significantly lower serum

autoantibody titres and decreased proteiuniria compared to WT NZM2410 mice. Autophagy inhibitors high throughput screening Fli-1+/− NZM2410 mice survived significantly longer compared to WT NZM2410 mice (unpublished data). However, Green et al.[25] demonstrated recently that non-haematopoietic factors also contribute to lupus disease development in the α-mannosidase II-deficient mice model. We believe that our data also support an effect of non-haematopoeitic cells on MRL/lpr mice disease development based on the decreased disease in the Fli-1+/− MRL/lpr mice receiving BM from WT MRL/lpr mice. Using mice with specific cell Fli-1 disruption will provide further insight into how Fli-1 affects lupus disease development. We are now generating conditional Fli-1 knock-out MRL/lpr mice for future study. In summary, our data demonstrate that the expression of Fli-1

in BM derived haematopoietic cells has a significant effect on autoimmune disease development in MRL/lpr mice and that decreased expression of Fli-1 in non-haematopoietic cell lineages also probably contributes to the improvement of autoimmune disease development in MRL/lpr mice, These data also indicate that the expression of a single gene in different cell types can have separate but synergistic effects on disease development. This study Thiamet G was supported by National Institutes CHIR-99021 of Health grants (AR054546 to X. K. Z.) and the Medical Research Service, Department of Veterans Affairs (to X. Z. and G. G.). None. “
“Sjögren’s syndrome (SS) is an autoimmune inflammatory disease that primarily affects the lacrimal and salivary glands causing dry eyes and mouth. Antibodies to Ro60 are frequently observed in patients with SS; however, the role of these antibodies in SS initiation and progression remains

unclear. The sequence Ro60 273-289 (Ro274) is a known B cell epitope of Ro60and antibodies to this epitope have been observed in a subset of SS patients and in animals immunized with Ro60 protein. Animals immunized with Ro274 linear peptide develop a Sjögren’s-like illness. We hypothesized that passive transfer of anti-Ro274-specific IgG would induce a Sjögren’s-like phenotype. To evaluate this hypothesis, we adoptively transferred affinity-purified Ro274 antibodies into naïve BALB/c animals then evaluated salivary gland histology, function and IgG localization four days post-transfer. At this timepoint, there was no demonstrable mononuclear cell infiltration and salivary glands were histologically normal, but we observed a functional deficit in stimulated salivary flow of animals receiving Ro274 antibodies compared to animals receiving control IgG.