The goal of this project is to understand how the interactions between cell surface receptors and their ligands affect cellular functions in the immune system. In particular, we are interested in how inhibitory receptors control immune cell responses. Inhibitory receptors act as a govenor on the immune response to avoid hyper inflammatory reactions that can potentiate autoimmunity. Two recently described inhibitory receptors are leukocyte-associated Ig-like receptor-1 (LAIR-1, also known as CD305) and IRp60 (also known as CD300a, LMIR1, CMRF35H). Both LAIR-1 and IRp60 are expressed by many cell types, including T, B and NK cells, mast cells, neutrophils, eosinophils, monocytes/macrophages, dendritic cells and stem cells. The ligand for LAIR-1 has recently been established as collagen(s), while the ligand for IRp60 is unknown. In vitro studies have shown that both receptors are able to down-regulate activation signals. So far, we have published that LAIR-1 is expressed differentially in several subsets of human T cells, with naive T cells expressing the highest amounts and that its ligation can inhibit T cell receptor (TCR) mediated calcium release and killing. We have shown that IRp60 is expressed very early during the granulocyte development and that it is very highly expressed in peripheral blood neutrophils. Stimulation with GM-CSF and LPS induces the translocation of an intracellular pool of IRp60 to the cell surface of neutrophils. While IRp60 can not inhibit LPS and fMLP mediated reactive oxygen species (ROS) production, it inhibits the Fc?RIIa mediated ROS production in calcium mediated manner. In addition to that, in vivo studies have shown that IRp60 ligation can inhibit IgE mediated mast cell degranulation and recruitment of eosinophils and mast cells into the peritoneum in a model of allergic peritonitis.
