IL1RII

Interleukin-1 receptor type II (IL-1RII), also known as CD121b, is a member of the interleukin-1 receptor family. It is a non-signaling receptor that binds interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β) with high affinity, acting primarily as a decoy receptor to dampen IL-1–mediated signaling. Unlike the signaling-competent IL-1 receptor type I (IL-1R1), IL-1RII lacks a cytoplasmic signaling domain, so ligand binding does not initiate the downstream MyD88/TIR inflammatory cascade.

Structurally, IL-1RII is a single-pass type I transmembrane protein with an extracellular region composed of three immunoglobulin-like domains. In addition to the membrane-bound form, a soluble form (sIL-1RII) arises from proteolytic shedding of the extracellular domain or alternative splicing, and can bind IL-1 in the circulation to modulate activity.

Expression of IL-1RII is broad, including monocytes, neutrophils, T and B lymphocytes, dendritic cells, and endothelial cells. Its distribution and regulation position IL-1RII as an important modulator of inflammatory responses, helping to limit excessive IL-1 activity during infection or tissue injury.

The IL1R2 gene encodes this receptor. Clinical relevance of IL-1RII includes observed alterations in inflammatory and autoimmune conditions, and soluble IL-1RII has been explored as a biomarker and therapeutic concept, complementing therapies that target IL-1 signaling.