SAT0005 Interleukin-33 ameliorates murine lupus via induction of regulatory t cells and m2 macrophage polarisation

Background The levels of IL-33, a Th2 promoting cytokine, and the soluble form of its receptor ST2 were reported to be elevated in serum of patients with active systemic lupus erythematosus (SLE), suggesting a role of the IL-33/ST2 axis in the pathogenesis of SLE. Objectives This study aims to examine the effect of IL-33 in disease severity of murine lupus. Methods IL-33 was injected intraperitoneally 3 times per week to pre-diseased MRL/lpr mice aged 12 weeks for 6 weeks. Control group was given 1% BSA injection. Urine protein was monitored weekly by albustix and protein assay. Immunophenotyping of splenocytes was examined by flow cytometry. Splenic CD11b+monocytic cells were isolated by microbeads for mRNA examination. Results IL-33-treated mice (n=9) developed significantly less proteinuria compared to BSA-treated group (n=9). Kidney histology of the IL-33-treated group showed remarkably less mesangial deposit, diffuse proliferative glomerular changes and crescents, and had significantly lower renal composite score compared to controls (median 2.0 vs 9.9, p Conclusions Exogenous IL-33 led to significantly less proteinuria and renal inflammation. These mice had significantly higher splenic Treg cells with prominent Foxp3 expression. Isolated CD11b+cells from spleen and kidney extracts demonstrated mRNA levels of M2 macrophage polarisation. Disclosure of Interest None declared