Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with no known cure. Current therapies primarily rely on symptom control with corticosteroids, however these therapies carry many adverse effects. In recent decades, the gut microbiome has gained appreciation as a major immunomodulator of autoimmune disease. Toll-like receptor 9 (TLR9) is known to interact with microbial DNA readily provided by the gut microbiota. Polymorphisms of TLR9 have been implicated in increased susceptibility to SLE, and overexpression of the receptor has been shown to be protective in mice. Agonization of TLR9 with bacterial DNA (bDNA) could provide a passive immunity to lupus and other autoimmune conditions without the side effects of corticosteroids.

We previously showed that in vivoadministration of bDNA was protective against lupus in mice, however the mechanism behind this protection was unknown. In vitrostimulation of lupus prone splenocytes showed increased production of IL-10, a potent anti-inflammatory cytokine, along with an increase in IL-6, a cytokine known to induce the proliferation of IL-10 producing B cells and antibody producing plasma cells. This phenomenon is dependent on TLR9 expression, but expression of TLR9 on either B cells or dendritic cells is sufficient to increase IL-10. However, TLR9 activation on B cells may cause an increase in IL-10 with a less dramatic increase in IL-6, which may lead to a more beneficial, anti-inflammatory profile as a potential therapeutic.

Our results suggest bDNA as a possible anti-inflammatory avenue of autoimmune management that avoids the use of corticosteroids. Future studies will focus on B cell targeted delivery of bDNA that promotes IL-10 without the side effect of increasing IL-6.

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