The available therapies for anti-myeloperoxidase (MPO) glomerulonephritis (GN) are broadly immunosuppressive and associated with serious adverse effects, particularly infections. A potentially safer approach is to specifically target anti-MPO immunity to restore tolerance to this autoantigen without compromising the immune response to pathogens. Now, Dragana Odobasic and colleagues report that tolerogenic dendritic cells (DCs) induced MPO-specific immunosuppression and attenuated anti-MPO GN in a mouse model.

“We chose to investigate tolerogenic DCs because they have a unique capacity to induce antigen-specific immunosuppression by presenting antigens to T cells, and because phase I trials have proven their feasibility and safety as a potential therapeutic approach in patients with various autoimmune diseases,” explains Odobasic. To generate tolerogenic DCs that specifically inhibit anti-MPO autoimmunity, the researchers cultured DCs with a NF-κB inhibitor to induce an anti-inflammatory phenotype and then exposed them to MPO. “These MPO-loaded tolerogenic DCs can present MPO and thus turn off disease-driving MPO-specific T cells,” says Odobasic.

Injection of the MPO-loaded DCs induced inhibitory IL-10-producing regulatory T cells in MPO-immunized mice and suppressed established anti-MPO autoimmunity, glomerular injury and proteinuria in mice with anti-MPO GN. The DCs did not inhibit immunity against an irrelevant antigen, confirming that their immunosuppressive effects were MPO-specific.

“These studies will pave the way for progress of MPO-presenting tolerogenic DCs into clinical trials,” concludes Odobasic. “By turning off anti-MPO autoimmunity, this therapy comes as close as possible to a cure for anti-MPO GN and has the potential to provide immense benefit to patients by enabling them to avoid complications resulting from the non-antigen-specific effects of current therapies.”