Leukocyte immunoglobulin-like receptor subfamily B member 3 (LILRB3)

Leukocyte immunoglobulin-like receptor subfamily B member 3 (LILRB3) is a type I transmembrane glycoprotein belonging to the leukocyte immunoglobulin-like receptor family. It is encoded by the LILRB3 gene located on chromosome 19q13.4. The protein contains four extracellular immunoglobulin domains and cytoplasmic ITIMs that mediate inhibitory signaling upon ligand binding. LILRB3 is expressed primarily on myeloid lineage cells—including monocytes, neutrophils, eosinophils, basophils—and mast cell progenitors. It acts as a critical regulatory checkpoint by inhibiting excessive activation of these cells and modulating inflammatory responses and cytotoxicity. Functionally relevant ligands include class I MHC antigens and complement components C3b/iCb/C4b/Cd/dgC8-associated cytokeratin fragments from necrotic tumor cells. Activation leads to recruitment of phosphatases such as SHP-1 via ITIMs resulting in suppression of downstream signaling pathways involved in inflammation and immune activation. Recent studies highlight its role not only in controlling innate immunity but also its potential involvement in cancer biology through interactions with ligands exposed on necrotic tumor cells. Its precise biological roles continue to be elucidated due partly to challenges distinguishing it from closely related family members like LILRA6 using antibodies.

Other names

ILT5LIR3CD85a

Inhibition of myeloid cell activation: Upon ligation or coligation with other immune receptors (e.g., FCGR2B), LILRB3 inhibits signaling through immunoreceptor tyrosine-based inhibitory motifs (ITIMs), recruiting phosphatases such as SHP-1 to dampen immune responses. Modulation of neutrophil effector functions: Inhibits Fc receptor–mediated ROS production, phagocytosis, and microbial killing in neutrophils. Inhibition of osteoclast differentiation: Blocks RANKL/TRANCE or M-CSF induced differentiation.