TLR3

Toll-like receptor 3 (TLR3), also designated as CD283, is a transmembrane protein crucial in innate immunity. It recognizes double-stranded RNA (dsRNA) structures derived from viral pathogens or endogenous sources, triggering downstream signaling via the TIR-domain-containing adapter-inducing interferon-β (TRIF) pathway. This activates transcription factors IRF3 and NF-κB, inducing type I interferons (IFNs) and pro-inflammatory cytokines. TLR3 operates within antiviral defense pathways and intersects with autophagy-related mechanisms. Dysregulation of TLR3 is implicated in viral susceptibility, autoimmune disorders (e.g., systemic lupus erythematosus), and neuroinflammatory conditions.
Therapeutic targeting of TLR3 includes agonists like polyinosinic-polycytidylic acid (Poly I:C), evaluated as adjuvants in cancer immunotherapy and antiviral vaccines. However, excessive TLR3 activation may exacerbate cytokine storms, prompting research into antagonists for inflammatory diseases. Small-molecule inhibitors (e.g., CU-CPT12a) and monoclonal antibodies are under preclinical investigation. Recent trials explore TLR3 modulation in COVID-19 and glioblastoma, highlighting its dual role as a therapeutic ally and pathological contributor. Drug development focuses on balancing immunostimulation and control of hyperactivation-related toxicity.