Title: AB0161 Interleukin-37: a therapeutic for lupus nephritis in mrl-faslpr mice
Abstract: <h3>Background</h3> Systemic lupus erythematosus (SLE) is a serious and noticed autoimmune disease, and lupus nephritis (LN) as one of its major complications without effective treatment. IL-37 has been identified as a natural inhibitor of innate immunity. Although increasing evidence shown that serum IL-37 correlated with SLEDAI and nephritis activity, However, it is still unclear that the therapeutic effect of IL-37 on lupus mice <i>in vivo</i>. <h3>Objectives</h3> This study aims to determine the inhibitory effect of IL-37 in lupus mice and lupus nephritis <i>in vivo</i>, and to expose the IL-37 related mechanisms of cell and molecules that inhibits the inflammmation in lupus nephritis. <h3>Methods</h3> MRL-Fas<sup>lpr</sup> mice with mild and advanced disease were treated with lentiviral vector pLVX-IL-37b. The protein levels of IL-37b in serum and tissue, IL-17, IL-6, IL-10 and TGFβ-3 produced by cell culture from spleen and kidney of mice were measured by ELISA, the relative mRNA expression of these cytokines in PBMCs was detected by RT-PCR, and the frequency of Th17 and Treg cells in splenocyte were determined by FACS. <h3>Results</h3> Our results show that IL-37 was highly effective in prolonging survival, alleviating the pathologic characteristics of lupus nephritis (LN) in MRL-Fas<sup>lpr</sup> mice by reducing the autoimmune complex deposition such as IgM, IgG and C3, decreasing the production of Inflammatory cytokines such as IL-17, IL-6 and promoting the anti-inflammatory cytokines IL-1 0and TGFβ-3. We also found that IL-37 protect lupus mice from LN associated with increasing the frequency of Treg cells and reducing the frequency of Th17 cells. <h3>Conclusions</h3> These results indicate the protective action of IL-37 in LN, and strengthen the support for IL-37 as a new target for therapy of SLE. <h3>Disclosure of Interest</h3> None declared