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

Alessandro Poggi, Elena Tomasello, Elisabetta Ferrero, Maria Raffaella Zocchi, Lorenzo Moretta

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)2086-2091
Number of pages6
JournalEuropean Journal of Immunology
Volume28
Issue number7
DOIs
Publication statusPublished - Jul 1998

Keywords

  • Calcium
  • Dendritic cell
  • Differentiation
  • Granulocyte-macrophage colony-stimulating factor receptor
  • LAIR-1

ASJC Scopus subject areas

  • Immunology

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