Immune-like transcript 5 (ILT5), also known as leukocyte immunoglobulin-like receptor subfamily B (LILRB3), leukocyte immunoglobulin-like receptor 3 (LIR3), and CD85a, is a member of the Ig-like receptor family involved in immune regulation. ILT5 belongs to the B subfamily, whose members have a cytoplasmic tail containing inhibitory sequences based on immunoreceptor tyrosine-based inhibitory motifs (ITIM), capable of inhibiting signaling events through the phosphatase SHP-1.
The counterpart of subfamily B is subfamily A, whose members act as activating receptors lacking ITIM, but signaling through association with FcRγ. ILT shares structural homology and chromosomal localization with the KIR receptor family.
In mice and rats, the LILRB3 gene encodes the PIR-B protein with six Ig-like domains. Rodent PIR-B and human ILT5 share 55% aa sequence identity within the common region of their ECD. Both PIR-B and ILT5 are receptors for Staphylococcus aureus, and bacterial activation of these receptors affects the innate immune response triggered by TLR.
ILT5 is expressed on the surface of peripheral monocytes, neutrophils, eosinophils, basophils, and mast cell precursors but not on mature mast cells. On basophils, crosslinking of ILT5 with the activating receptor ILT1/LIR7 Fc epsilon RI inhibits the release of histamine, leukotriene C4, and IL-4. Binding of ILT5 on osteoclast precursors inhibits RANKL- or M-CSF-induced differentiation. After successful treatment with DMARD rheumatoid arthritis drugs, ILT5 is downregulated on macrophages in synovial tissue.
