PTPN22 and autoimmune disease: These three mechanisms can negatively regulate TLR-mediated immune response and influence the pathogenesis and treatment of autoimmune diseases.19–21 LYP in mononuclear cells can downregulate the activity of TLRs, and LYP inhibits TLR responses through the inhibition of the TREM2/DAP12 pathway.22 In aggregate, TLR activation can be a double-edged sword to the well-being of an organism.