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Toll-like receptor 7 (TLR7) and toll-like receptor 9 (TLR9) are endosomal pattern recognition receptors crucial to the innate immune response, primarily recognizing single-stranded viral RNA (TLR7) and unmethylated CpG-rich DNA (TLR9)[3][5]. They are expressed in various immune cells, notably plasmacytoid dendritic cells and B cells, and signal through a MyD88-dependent pathway to induce the production of type I interferons and pro-inflammatory cytokines[2][3][7]. TLR7 and TLR9 play a dual role: defending against pathogens as well as contributing to pathogenesis in autoimmune diseases such as systemic lupus erythematosus by regulating B cell activation and autoantibody production[2][7]. Several small-molecule agonists and antagonists have been developed to modulate their activity for therapeutic purposes, but their clinical use is complicated by the risk of immune overactivation and infection susceptibility[1][6].
Agonists: activate receptor dimerization and MyD88-dependent signaling, leading to cytokine release and immune cell activation. Antagonists: prevent functional dimerization or maintain inactive conformations, reducing cytokine production and dampening immune activation. DNA or RNA ligand binding triggers distinct downstream signaling based on receptor localization (endolysosomal versus other compartments).
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