Signalregulatory

Signal-regulatory proteins, commonly abbreviated as SIRPs, are a family of transmembrane receptors in the immunoglobulin superfamily that regulate signaling in immune and other cell types. In humans, principal members include SIRP alpha (SIRPA), SIRP beta (SIRPB1), and SIRP gamma (SIRPG). They are expressed on myeloid cells such as macrophages and dendritic cells and, in some tissues, on neurons and other cell types. SIRPs generally feature extracellular immunoglobulin-like domains, a single transmembrane region, and cytoplasmic ITIM motifs that recruit phosphatases such as SHP-1 and SHP-2 when phosphorylated.

A key function is to dampen cellular activation. The interaction of SIRP alpha with the widely expressed ligand CD47 transduces a "don’t eat me" signal that limits phagocytosis of self-cells and modulates antigen presentation and inflammation. Through ITIM-based signaling, SIRPs regulate adhesion and migration and can influence cytokine production in various contexts.

Clinical relevance: The CD47-SIRP alpha axis is a focus of cancer immunotherapy. Many cancers upregulate CD47 to escape macrophage clearance, and therapeutic approaches that block this interaction aim to promote tumor phagocytosis. Altered SIRP signaling has also been studied in autoimmunity and neuroimmune regulation, though tissue- and context-specific effects remain under study.