IL1RL1
Description
The IL1RL1 (interleukin 1 receptor like 1) is a protein-coding gene located on chromosome 2.
IL1RL1, also known as ST2, is a protein encoded by the IL1RL1 gene. It is a member of the Toll-like receptor superfamily based on its intracellular TIR domain, but its extracellular region is composed of immunoglobulin domains. Unlike other members of the family, IL1RL1 does not induce an inflammatory response through activation of NF-κB, although it does activate MAP kinases. ST2 has two isoforms: a soluble form (sST2) and a membrane-bound receptor form (ST2L). When the myocardium is stretched, the ST2 gene is upregulated, increasing the concentration of circulating sST2. The ligand for ST2 is the cytokine IL-33. Binding of IL-33 to the ST2 receptor, in response to cardiac disease or injury, elicits a cardioprotective effect. This cardioprotective IL-33 signal is counterbalanced by the level of sST2, which binds IL-33 and makes it unavailable to the ST2 receptor for cardioprotective signaling. As a result, the heart is subjected to greater stress in the presence of high levels of sST2.
IL1RL1 is a receptor for interleukin-33 (IL-33) that plays crucial roles in innate and adaptive immunity. It contributes to tissue homeostasis and responses to environmental stresses together with coreceptor IL1RAP. Stimulation of IL1RL1 recruits MYD88, IRAK1, IRAK4, and TRAF6, followed by phosphorylation of MAPK3/ERK1 and/or MAPK1/ERK2, MAPK14, and MAPK8. It is possibly involved in helper T-cell function. Upon tissue injury, IL1RL1 induces UCP2-dependent mitochondrial rewiring, which attenuates the generation of reactive oxygen species and preserves the integrity of the Krebs cycle, required for persistent production of itaconate and subsequent GATA3-dependent differentiation of inflammation-resolving alternatively activated macrophages.
IL1RL1 is also known as DER4, FIT-1, IL33R, ST2, ST2L, ST2V, T1.
