TLR4 and adult-onset Still disease: As for the roles of TLRs and their ligands in activation of monocytes/macrophages in AOSD, interaction between various DAMPs and TLRs, including S100 proteins with TLR4, high mobility group box-1 (HMGB1) with TLR4 and RAGE, and nucleic acids with TLR7, has been identified (19, 52).