LIRs/ILTs/MIRs, inhibitory and stimulatory Ig-superfamily receptors expressed in myeloid and lymphoid cells.

Cells exhibit a complex network of inhibitory and stimulatory signaling pathways, which interact with each other to maintain an homeostatic balance and modulate cellular responses to external stimuli. During most of the 1980s, a great effort was put into the characterization of stimulatory cell surface receptors for cytokines and growth factors. In the last decade, a large number of inhibitory receptors have been identified and it has become apparent that inhibitory signaling pathways are subject to intricate regulatory mechanisms. Inhibitory and stimulatory signaling pathways work in concert with each other to establish activation thresholds and provide sensitive tuning mechanisms that help control cellular responses. LIRs/ILTs/MIRs are a novel family of inhibitory and stimulatory receptors expressed both in myeloid and lymphoid cells. They contain two or four immunoglobulin-like domains in the extracellular region and their cytoplasmic domains are either very short and without any signaling motifs or are long and contain a variable number of immunoreceptor tyrosine-based inhibition motifs (ITIMs). LIRs within the first group send stimulatory signals by association with the FcR common gamma chain and LIRs within the second group deliver inhibitory signals by association with the protein tyrosine phosphatase SHP-1. This review summarizes our current knowledge on the LIRs, their ligands, and biological functions.