TLR7/8 Activation in Immune Cells and Muscle by RNA-Containing Immune Complexes: Role in Inflammation and the Pathogenesis of Myositis.

Objective: Activation of endosomal toll-like receptors (TLRs) is one possible driver of inflammation in idiopathic inflammatory myopathies (IIM). We investigated the potential contribution of TLR7 and TLR8 to IIM pathogenesis.

Methods: Activation of TLR7/8 in healthy donor peripheral blood mononuclear cells (PBMCs) by immune complexes from patients with IIMs and lupus was tested.

Discovery of M5049: A Novel Selective Toll-Like Receptor 7/8 Inhibitor for Treatment of Autoimmunity.

Toll-like receptor (TLR) 7 and TLR8 are transmembrane receptors that recognize single-stranded RNA. Activation of these receptors results in immune cell stimulation and inflammatory cytokine production, which is normally a protective host response. However, aberrant activation of TLR7/8 is potentially pathogenic and linked to progression of certain autoimmune diseases such as lupus.