IL1RL1/ST2 Fc Chimera Protein, Human

ST2,also known as IL-1 R4 and T1, is an Interleukin-1 receptor family glycoproteinthat contributes to Th2 immune responses. Human ST2 consists of a 310 aminoacid (aa) extracellular domain (ECD) with three Ig-like domains, a 21 aatransmembrane segment, and a 207 aa cytoplasmic domain with an intracellularTIR domain. ST2 is expressed on the surface of mast cells, activated Th2 cells,macrophages, and cardiac myocytes. It binds IL-33, a cytokine that isupregulated by inflammation or mechanical strain in smooth muscle cells, airwayepithelia, keratinocytes, and cardiac fibroblasts. IL-33 binding induces theassociation of ST2 with IL-1R AcP, a shared signaling subunit that alsoassociates with IL-1 RI and IL-1 R rp2. In macrophages, ST2 interferes withsignaling from IL-1 RI and TLR4 by sequestering the adaptor proteins MyD88 andMal. In addition to its role in promoting mast cell and Th2 dependentinflammation, ST2 activation enhances antigen induced hypernociception andprotects from atherosclerosis and cardiac hypertrophy. Upon tissue injury,induces UCP2-dependent mitochondrial rewiring that attenuates the generation ofreactive oxygen species and preserves the integrity of Krebs cycle required forpersistent production of itaconate and subsequent GATA3-dependentdifferentiation of inflammation-resolving alternatively activated macrophages.