Toll-like receptor 7 (TLR7) and Toll-like receptor 8 (TLR8) (TLR7/8)

Toll-like receptor 7 (TLR7) and Toll-like receptor 8 (TLR8) are endosomal pattern recognition receptors that serve as critical sensors of the innate immune system by detecting single-stranded RNA (ssRNA) from viral and bacterial pathogens (UniProt P87667, Q9NRG1). Located primarily in the endosomes of immune cells such as plasmacytoid dendritic cells and monocytes, these receptors trigger the MyD88-dependent signaling pathway to produce Type I interferons and pro-inflammatory cytokines (PubMed: 12444136). In the context of oncology, TLR7/8 agonists are developed as immunotherapeutic agents to stimulate anti-tumor T-cell responses and modify the tumor microenvironment (PubMed: 27117459). Conversely, the inappropriate recognition of self-RNA by TLR7 and TLR8 is a major driver of autoimmune pathogenesis, particularly in systemic lupus erythematosus (SLE), making these receptors key targets for antagonistic therapies (PubMed: 30104475). The therapeutic window for agonists is often limited by the risk of systemic cytokine-mediated toxicity, necessitating localized delivery or highly specific dosing strategies (PubMed: 32636255).

Other names

TLR7TLR8CD287CD288Toll-like receptor 7/8 complex

Agonists bind to the endosomal binding pockets of TLR7 and/or TLR8, inducing receptor dimerization and the recruitment of the adapter protein MyD88, which initiates a signaling cascade involving IRAK kinases and TRAF6, ultimately activating NF-kappaB and IRF7 to drive the transcription of pro-inflammatory cytokines and Type I interferons (PubMed: 24336201). Antagonists work by competitively inhibiting the binding of endogenous or exogenous RNA ligands to these receptors, thereby suppressing the pathological immune activation seen in autoimmune disorders (PubMed: 30104475).