Inhibition of TLR4 signaling protects mice from sensory and motor dysfunction in an animal model of autoimmune peripheral neuropathy

Abstract Background While the etiology remains elusive, macrophages and T cells in peripheral nerves are considered as effector mediating autoimmune neuropathy (APN), such Guillain-Barre syndrome. By recognizing both pathogen-associated molecular patterns (PAMPs) damage-associated (DAMPs) signals, TLRs play a central role initiation of innate adaptive immune responses. In this study, we aimed to understand involvement TLR4 pathogenesis APN explore potential drug target for therapeutic use. Methods was induced by partial ligation on one sciatic B7.2 (L31) transgenic mice which possess predisposed inflammatory background. pathology neurological function were evaluated other non-injured nerve. Results its endogenous ligand HMGB1 highly expressed L31 mice, circulating nerves. Enhanced signaling blocked with TAK 242, selective inhibitor, before after disease onset. Intraperitoneal administration 242 not only inhibited monocyte, macrophage CD8 + cell activation, but also reduced release pro-inflammatory cytokines. protected from severe myelin axonal loss, resulting remarkable improvement mouse motor sensory functions. effective alleviating preventive reversal paradigms. Conclusion The study identified critical contribution TLR4-mediated activation course provided strong evidence support useful treating neuropathy.