Reduction of autoantibody in SLE by probiotic exopolysaccharide-induced inhibitory dendritic cells

Abstract

Abstract Exopolysaccharide (EPS) secreted by a commensal bacterium, Bacillus subtilis, induces alternatively-activated, anti-inflammatory M2 macrophages that protect mice from T cell-dependent inflammatory disease induced by the enteric pathogen Citrobacter rodentium. We tested the activity of EPS on dendritic cells (DCs), and found that in vitro, EPS not only induced the expression of inhibitory molecules, PDL1 and PDL2, but also that these DCs inhibited alloreactive T cell activation and proliferation in mixed lymphocyte reactions (MLR). We also found that in vivo injection of EPS resulted in the generation of DCs expressing PD-L1 and PD-L2. To test if the EPS-induced DCs are inhibitory in vivo, we used a model that mimics Systemic Lupus Erythematosus (SLE) and tested if the level of autoantibody was decreased. We injected Bm12 cells into EPS-treated C57BL/6 mice to induce SLE-like symptoms, and found that the titer of autoantibodies was significantly decreased in the EPS-injected mice compared to control mice. We conclude that EPS can generate inhibitory DCs both in vitro and in vivo, and we suggest that these DCs have the potential to protect from SLE and other autoimmune diseases.