Toll-like receptor 8 (TLR8) (TLR8)

Human Toll-like receptor 8 (TLR8) is a member of the Toll-like receptor family that plays a fundamental role in pathogen recognition and the activation of innate immunity. It is an endosomal receptor primarily expressed in myeloid cells, such as monocytes, macrophages, and dendritic cells, where it functions as a sensor for single-stranded RNA (ssRNA) derived from viruses and bacteria [7, 12, 13]. Upon ligand binding, TLR8 undergoes a conformational change that recruits the adapter protein MyD88, initiating a signaling cascade that activates transcription factors like NF-kappaB and IRF5 [12, 13]. This process leads to the robust production of pro-inflammatory cytokines, including IL-12, TNF-alpha, and Type I interferons, which are essential for orchestrating both innate and adaptive immune responses [1, 11, 12]. In the context of disease, TLR8 is a significant therapeutic target for cancer and chronic infectious diseases. TLR8 agonists, such as selgantolimod and motolimod, are being investigated for their ability to stimulate anti-tumor immunity and promote the functional cure of chronic Hepatitis B by enhancing the activity of natural killer cells and cytotoxic T lymphocytes [1, 2, 11]. Conversely, overactivation of TLR8 has been implicated in the pathogenesis of autoimmune disorders like systemic lupus erythematosus and rheumatoid arthritis, leading to the development of TLR8 antagonists as potential anti-inflammatory therapies [4, 7]. However, systemic administration of TLR8 agonists poses safety challenges, including the risk of cytokine release syndrome and gastrointestinal toxicities, necessitating careful dose management or localized delivery strategies [1, 6, 11].

Other names

CD288TLR8Toll-like receptor 8

Agonist (activates TLR8 to induce pro-inflammatory cytokines and enhance innate/adaptive immunity); Antagonist (inhibits TLR8 to reduce excessive inflammation in autoimmune diseases) [1, 4, 5, 11, 12]