TLR6

TLR6 functions as a cell-surface pattern-recognition receptor by forming the TLR2/6 heterodimer, which recognizes di-acylated lipopeptide signals and initiates innate immune activation^[1]. Mechanistically, TLR2/6 signaling activates NF-κB-dependent inflammatory pathways, leading to cytokine outputs such as IL-6, IL-1β, and TNF-α in experimental cell models^[2]. In disease models, TLR6 variants were identified in Kawasaki disease susceptibility, and TLR6 rs56245262 genotype was associated with differential IL-6 expression and higher erythrocyte sedimentation rate^[3]. Compared with TLR1/2, TLR2/6 shows heterodimer-specific biology: Pam2CSK4, but not Pam3CSK4, accelerated leukemia and death in an NHD13 mouse model of myelodysplastic syndrome^[4]. For experimental applications, FSL-1 and Pam2CSK4 serve as TLR2/6 agonists, while sensitive NF-κB reporter platforms detect TLR2/6 ligands at low concentrations for ligand characterization^[5].