Using a mouse model of systemic lupus erythematosus (SLE), we recently demonstrated that Interferon regulatory factor (IRF)7-deficient mice developed glomerulonephritis but failed to develop autoantibody production. We suggested that the type I Interferon (IFN) pathway is critical for autoantibody production but the NF-kB activation is sufficient for the development of glomerulonephritis. Here, we show IRF8-deficient mice failed to develop both glomerulonephritis and autoantibody production. We demonstrate that Ly6Chi inflammatory monocytes were recruited to the peritoneal cavity in wild-type and IRF7-deficient mice but not in IRF8-deficient mice. Ly6Chi monocytes produced proinflammatory cytokines and expressed IFN-stimulated genes in wild-type mice, while in IRF7-deficient mice they only produced proinflammatory cytokines. Ly6Chi monocytes migrated to spleen where they differentiated into dendritic cells (DC) capable of responding to dsDNA auto antigen. These monocyte-derived DC produced proinflammatory cytokines in response to dsDNA in wild-type mice. Collectively, type I IFN produced from monocyte-derived DC might be essential for autoantibody production and proinflammatory cytokines produced from inflammatory monocytes/ monocyte-derived DC might cause tissue damage in this model. Our study reveals a specialized role for monocyte-derived DC in autoimmunity. Plasticity of monocyte might play an important role not only in the pathogenesis of the disease but also in flare-ups of the disease.

Monocyte-derived dendritic cells mediate autoimmunity in murine model of systemic lupus erythematosus