Toll-like receptors 7 and 8 (TLR7/8) are intracellular nucleic acid sensors expressed across the immune system. TLR7 is expressed most predominantly on plasmacytoid dendritic cells (pDC) and B cells, while TLR8 is expressed on monocytes, macrophages and other myeloid cells. They evolved to detect viral and microbial RNA, but in autoimmune and chronic inflammation disease they are chronically activated by the body's own nucleic acids. Because TLR7 and TLR8 sit upstream of the type I interferon response, myeloid inflammation and pathogenic B-cell activity, dual antagonism of these receptors represents a broader upstream approach that has the potential to address the underlying drivers of interferon, myeloid inflammation - and autoantibody-mediated disease.

DCs produce large amounts of type I interferon, contributing to uncontrolled immune cell activation, tissue inflammation and the interferon signature observed across a range of autoimmune diseases. B cells are driven to differentiate towards antibody producing cells and increased production of autoantibodies that mediate tissue damage. Monocytes and macrophages release inflammatory mediators that sustain and amplify the response in affected tissue. A single receptor pair therefore sits upstream of both the innate and adaptive arms of the immune response.

Human genetics underlines both receptors. A single gain-of-function change in TLR7 is sufficient to cause systemic autoimmune disease, with lupus the best-characterized example, while the body of evidence for polymorphisms in TLR8 contributing to immune cell function continues to expand.