TLR8 on dendritic cells and TLR9 on B cells restrain TLR7-mediated spontaneous autoimmunity in C57BL/6 mice

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Abstract
Significance: Toll-like receptors (TLRs) that sense microbial or endogenous DNA and RNA have been well implicated in systemic lupus erythematosus (SLE), a multisystem disease characterized by an autoimmune response to nuclear antigens. In mice, both TLR8 and TLR9 control TLR7-mediated lupus, but it is unknown if they have an additive effect in controlling TLR7. We demonstrate that double TLR8/9-deficient mice have increased abnormalities characteristic of SLE and that both TLR8 and TLR9 keep under control TLR7-mediated lupus, but they act on different cell types. TLR8 controls TLR7 function on dendritic cells, and TLR9 restrains TLR7 response on B cells. These TLR interactions have to be taken into account when novel therapeutic approaches are developed that target the blocking of TLRs.

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