Toll-like receptor 7/8

Toll-like receptors 7 and 8 (TLR7 and TLR8) are single-stranded RNA (ssRNA)-sensing pattern recognition receptors (PRRs) belonging to the toll-like receptor family, a class of innate immune sensors critical for detecting pathogen-associated molecular patterns (PAMPs). Both receptors are endosomal transmembrane glycoproteins expressed predominantly on immune cells, including dendritic cells, monocytes, macrophages, and B cells. TLR7 is preferentially expressed in plasmacytoid dendritic cells, while TLR8 shows higher expression in myeloid dendritic cells and monocytes. Upon binding to viral ssRNA or synthetic agonists, TLR7 and TLR8 signal through the MyD88 adaptor protein, activating NF-κB and IRF transcription factors to drive production of proinflammatory cytokines such as Interleukin-6 (IL-6), type I interferons, and other innate immune mediators. Their combined designation as TLR7/8 reflects substantial functional overlap, as dual agonists capable of engaging both receptors — most notably resiquimod (R848) — are widely used in research and clinical development.

TLR7 and TLR8 occupy a central position at the intersection of innate and adaptive immunity. Their activation potently stimulates dendritic cell maturation, enhances antigen cross-presentation, and promotes Th1-polarized adaptive immune responses, properties that have made TLR7/8 agonists attractive as vaccine adjuvants and cancer immunotherapy agents. Conversely, dysregulated or excessive signaling through these receptors — particularly gain-of-function mutations in TLR7 — has been implicated in autoimmune conditions including systemic lupus erythematosus (SLE), positioning TLR7/8 antagonists as a complementary therapeutic avenue. The dual nature of TLR7/8 as both immune activators and drivers of immunopathology makes them high-value targets across oncology, infectious disease, and autoimmunity research.