A cell-penetrating peptide blocks Toll-like receptor-mediated downstream signaling and ameliorates autoimmune and inflammatory diseases in mice

Abstract

Inflammation: A decoy peptide treats arthritis and sepsis in mice A newly discovered peptide drug that disrupts signaling through a critical immune pathway could offer a new treatment for inflammatory diseases. Sangdun Choi from Ajou University in Suwon, South Korea, and colleagues designed the drug to look similar to—and thus act as kind of decoy for—a protein that regulates signaling through Toll-like receptors (TLRs), proteins found on immune cells that initiate responses to pathogens and also play a role in autoimmunity. In mouse and human cells, the drug inhibited multiple TLR signaling pathways, including a pathway that normally activates a multiprotein complex implicated in a variety of inflammatory diseases. In mouse models of rheumatoid arthritis and sepsis, the drug limited the release of proinflammatory molecules in the blood and reduced disease symptoms.