SIGIRR: An Orphan Receptor Mediating Anti-inflammatory Actions

SIGIRR, also known as the single immunoglobulin interleukin-1 receptor (IL-1R)-related molecule, is a member of the IL-1 receptor superfamily and is believed to play a pivotal role in inflammation and anti-inflammatory regulation within the body. Studies have shown that SIGIRR expression is associated with autoimmunity, inflammatory disorders, graft rejection, viral infection, thrombosis and tumour progression. Due to its unique structure and function, SIGIRR is commonly referred to as an 'orphan receptor', with IL-37 being the only confirmed ligand molecule for SIGIRR to date. The primary mechanism through which SIGIRR exerts its anti-inflammatory regulatory effect involves the negative modulation of the Toll-like receptor-IL-1R (TLR-IL-1R) signalling pathway. TLR-IL-1R signalling plays critical roles in immune responses triggered by microbial invasion and alterations in the tumour immune microenvironment. This article provides an overview of research findings on SIGIRR as an orphan receptor and its regulatory role in maintaining a delicate balance between natural immune activation and uncontrolled inflammatory processes under pathological conditions.