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 CD80bright and CD86bright) 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.
Poggi
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Laboratorio di Immunopatologia, Istituto Nazionale per la Ricerca sul Cancro e Centro di Biotecnologie Avanzate CBA-IST, Genova, Italy.
Tomasello
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Ferrero
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Zocchi
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MR
Moretta
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D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology*
D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D011971:Receptors, Immunologic; C108073:leukocyte-associated immunoglobulin-like receptor 1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002118:Calcium