Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
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A more recent version of this article appeared on June 1, 2005

Published online before print April 13, 2005
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0205090

Received for publication February 14, 2005.
Revised March 15, 2005.
Accepted for publication March 18, 2005.

Article

IRF-4 expression in the human myeloid lineage: up-regulation during dendritic cell differentiation and inhibition by 1{alpha},25-dihydroxyvitamin D3

Maria Cristina Gauzzi *, Cristina Purificato *, Lucia Conti *, Luciano Adorini {dagger}, Filippo Belardelli *, and Sandra Gessani *@

*Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Roma, Italy; and {dagger}BioXell, Milano, Italy

@ To whom correspondence should be addressed. E-mail: gessani{at}iss.it.


  Abstract

Interferon (IFN) regulatory factor (IRF)-4 is a lymphoid- and myeloid-restricted transcription factor of the IRF family. We analyzed its expression during differentiation of human monocytes along the macrophage or the dendritic cell (DC) pathway and in blood myeloid and plasmacytoid DC (M-DC and P-DC, respectively) subsets. Monocyte differentiation into DC, driven by granulocyte macrophage-colony stimulating factor (GM-CSF)/interleukin-4 or GM-CSF/IFN-{beta}, resulted in a strong up-regulation of IRF-4 mRNA and protein, which was further increased by lipopolysaccharide. It is interesting that 1{alpha},25-dihydroxyvitamin D3 [1,25(OH)2D3], a potent inhibitor of DC differentiation, completely abolished IRF-4 up-regulation. IRF-4 was also detected in blood P-DC and M-DC. However, up-regulation upon in vitro culture and down-regulation by 1,25(OH)2D3 was observed in M-DC but not in P-DC. These results point to IRF-4 as a potential player in human M-DC differentiation and as a novel target for the immunomodulatory activity of 1,25(OH)2D3.

Key Words: transcription factor • immunomodulator • gene regulation






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Copyright © 2005 by the Society for Leukocyte Biology.