p40/LAIR-1 regulates the differentiation of peripheral blood precursors to dendritic cells induced by granulocyte-monocyte colony-stimulating factor

p40/LAIR-1, a member of the immunoglobulin superfamily, is a surface molecule broadly distributed among leukocytes which has been shown to down-regulate T and NK cell activation. In this study, we show that p40/LAIR-1 is highly expressed in CD14⁺ peripheral blood mononuclear cells (PBMC). When cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) for 10 – 14 days, CD14⁺ cells acquired morphologic and phenotypic features ( i.e. loss of CD14 and expression of CD80^bright and CD86^bright ) typical of dendritic cells (DC) and lost the expression of p40/LAIR-1. Engagement of p40/LAIR-1 (but not of CD58) by specific monoclonal antibodies prevented CD14⁺ PBMC differentiation into DC; when cultured in the presence of GM- CSF upon p40/LAIR-1 cross-linking, the resulting cells were CD14⁺ CD80^dull CD86^dull and displayed a macrophage-like morphology. We have recently demonstrated that peripheral blood CD14⁺ cells co-expressing the CD34 progenitor marker represent the circulating precursors of CD83⁺ DC. Herein we show that cross-linking of p40/LAIR-1 prevented the maturation of CD14⁺ CD34⁺ cells into CD83⁺ DC. This effect appears to be consequent to the impairment of GM-CSF receptor-mediated activation signaling. Indeed, triggering of GM-CSF receptors in both CD14⁺ and CD14⁺ CD34⁺ cells led to increases in the intracellular free calcium concentrations which were inhibited by p40/LAIR-1 engagement. Taken together, these data suggest a possible regulating role played by p40/LAIR-1 in the process of differentiation from peripheral blood precursors into DC induced by GM-CSF.