Leukocyte-Associated Ig-Like Receptor 1 (LAIR-1) is a cell-surface molecule that functions as an inhibitory receptor on various immune cells. The mouse homologue of LAIR-1, often referred to as mLAIR-1, shares many similarities with its human counterpart and serves as a valuable model for studying immune regulation.
LAIR-1 is a type I transmembrane glycoprotein with a single Ig-like domain in the extracellular region and a cytoplasmic tail containing two immunoreceptor tyrosine-based inhibitory motifs (ITIMs) . These ITIMs are crucial for the inhibitory function of LAIR-1, as they recruit Src homology region 2-containing protein tyrosine phosphatase (SHP)-2, but not SHP-1 .
In mice, mLAIR-1 is expressed on the majority of immune cells, including T cells, NK cells, monocytes, and dendritic cells . It is inducibly expressed on blood granulocytes in vivo and is differentially expressed upon T cell activation in vitro . Interestingly, mLAIR-1 is not expressed on splenic and blood B220+ B cells .
LAIR-1 functions as an inhibitory receptor by interacting with collagen molecules. This interaction is hydroxyproline-dependent and involves synthetic collagen Gly-Pro-Hyp peptides . The binding of LAIR-1 to collagen inhibits CD3-induced T cell stimulation in vitro, highlighting its role in regulating immune responses .
The immune system relies on a balance between activating and inhibitory signals to function properly. Inhibitory signals, such as those mediated by LAIR-1, are essential for terminating immune responses and preventing excessive immune reactions or autoimmune diseases . The presence of ITIMs in the cytoplasmic tail of LAIR-1 allows it to recruit phosphatases like SHP-2, which dephosphorylate key signaling molecules and dampen immune cell activation .
Given its role in immune regulation, LAIR-1 has been investigated as a potential therapeutic target. Studies have shown that blocking the LAIR-1:collagen interaction can enhance anti-tumor responses in mice . For example, combining LAIR-1 blockade with programmed death-ligand 1 (PD-L1) targeting therapy has been shown to increase tumor control and improve survival in mouse models . This suggests that targeting the LAIR-1 pathway could be a promising strategy for cancer immunotherapy.