Published online before print April 13, 2005

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(Journal of Leukocyte Biology. 2005;77:944-947.)
© 2005 by Society for Leukocyte Biology

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

Maria Cristina Gauzzi^*, Cristina Purificato^*, Lucia Conti^*, Luciano Adorini, Filippo Belardelli^* and Sandra Gessani^*,1

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

¹ Correspondence: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. E-mail: gessani{at}iss.it

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-ß, resulted in a strong up-regulation of IRF-4 mRNA and protein, which was further increased by lipopolysaccharide. It is interesting that 1,25-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 myeloid 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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