The pathogenetic mechanisms that drive Systemic Lupus Erythematosus (SLE) are still merely understood. Recent genome-wide association studies have linked Tnipl, which encodes ABINI, with SLE. We identified ABINI as signaling component of Toll-like receptors (TLR), and studies of ABIN1-deficient mice revealed a lupus-like inflammatory disease with striking similarity to SLE. Innate immune cells use TLRs physiologically to initiate immune responses by pro-inflammatory mechanisms; however, data from SLE patients indicate that TLR-mediated inflammation may also contribute to disease. We show in this application (i) that disease in ABINI -deficient mice is mediated via MyD88, the master regulator of TLRs and (ii) that disease proceeds independent of T- and B-cells, Thus, this model is uniquely suited to investigate TLR-mediated, innate immune cell mechanisms contributing to inflammation* By using a defined set of genetic and biochemical experiments, we propose here to define (i) the role of suspected culprits, i.e. TLR7, TLR9 and type I interferons, (ii) the impact of specific ABINI -target genes, i.e. C/EBPß, G-CSF and INOS, (iii) the contribution of neutrophils and (iv) the molecular mechanism of ABINI -mediated gene regulation. We expect that information obtained will help to identify pathogenetically important factors contributing to inflammation, and hopefully identify promising therapeutic targets for SLE.