This co-regulation by CCRP may expand to other genes in future investigations. Hepatic steatosis and an increase in blood cholesterol levels suggest that CCRP may regulate diverse array of hepatic genes far beyond Cyp genes. Further investigations with KO mice should help us to understand CCRP biology and its molecular mechanisms. Apart from their role in anti-microbial defence, anti-microbial peptides such as the human cathelicidin LL-37 possess potent immunomodulatory properties and have recently also been implicated in the pathogenesis of autoimmune diseases. In sera of patients with Systemic Lupus Erythematosus, immune complexes of AMPs and self-DNA derived from neutrophil extracellular traps were reported to trigger activation of Tolllike receptor 9. Furthermore, SLE-patients were found to develop autoantibodies to both self-DNA and AMPs. Patients with SLE and a subset of RA patients display a type I interferon signature in their peripheral blood mononuclear cells. Given their reported role in SLE, AMPs may also stimulate TLR-pathways in other autoimmune diseases characterized by reactivity to nucleic acids, such as arthritis. In a previous study, we observed overexpression of LL-37 and its rat homologue rCRAMP in arthritic joints of patients with RA and of rats, respectively. In rat pristane-induced arthritis, the increased expression of rCRAMP coincided with the development of anti-rCRAMP autoAbs. We have now continued to further investigate the functional importance of cathelicidins, using sera from patient cohorts with SLE and RA and cathelicidindeficient mice. Although we detected autoAbs to cathelicidins in humans and in mice with lupus, they were not linked to disease activity or severity. Furthermore, in mouse models of arthritis and inducible lupus, cathelicidin-deficient mice developed a disease comparable in severity to wild type animals. Our results therefore do not support previous reports about an indispensable role of cathelicidins in the pathogenesis of lupus and arthritis. Complexes with DNA induced a significant induction of IFNa production only in human cells. DAPT Considering that in PIL, monocytes have been described as the main producers of IFNa we also used whole blood from WT and CRAMP-deficient mice for our stimulation experiments. However, IFNa production was not significantly enhanced by stimulation with DNA-CRAMP-complexes. Thus, in our hands CRAMP shows similar capacity as LL-37 to stimulate IFNa production via complexation to RNA. However, the effect is much lower than previously described and complexation with DNA does not significantly induce IFNa production in mouse cells. To address the second described mechanism, we incubated mouse blood from nai¨ve WT mice with IgG isolated from serum of healthy mice and mice with PIL. After erythrocyte lysis, we prepared cytospins and stained them with a DNA-dye and an antibody to neutrophil elastase. As a control we also used blood cells stimulated with a polyclonal anti-CRAMP antibody, with PMA, a well-known inducer of NETosis, and unstimulated blood cells.