Journal of Leukocyte Biology
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Originally published online as doi:10.1189/jlb.0205083 on October 21, 2005

Published online before print October 21, 2005
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(Journal of Leukocyte Biology. 2006;79:173-183.)
© 2006 by Society for Leukocyte Biology

The interferon-inducible gene, Ifi204, is transcriptionally activated in response to M-CSF, and its expression favors macrophage differentiation in myeloid progenitor cells

Jérémy Dauffy, Guy Mouchiroud and Roland P. Bourette1

Centre de Génétique Moléculaire et Cellulaire, UMR CNRS 5534, Villeurbanne Cedex, France

1 Correspondence: Centre de Génétique Moléculaire et Cellulaire, UMR CNRS 5534, 16 Rue Dubois, 69622 Villeurbanne Cedex, France. E-mail: bourette{at}biomserv.univ-lyon1.fr

The interferon-inducible (Ifi)204 gene was isolated as a macrophage-colony stimulating factor (M-CSF)-responsive gene using a gene trap approach in the myeloid interleukin-3 (IL-3)-dependent FD-Fms cell line, which differentiates in macrophages in response to M-CSF. Here, we show that Ifi204 was transcriptionally activated in response to M-CSF, and FD-Fms cells decreased their growth and committed toward a macrophage morphology; this induction was abrogated when the differentiation signal of the M-CSF receptor was blocked; the Ifi204 gene was also induced during macrophage differentiation controlled by leukemia inhibitory factor; and the Ifi204 gene is expressed in different mature monocyte/macrophage cells. Finally, we showed that enforced expression of Ifi204 strongly decreased IL-3- and M-CSF-dependent proliferation and conversely, favored macrophage differentiation of FD-Fms cells in response to M-CSF. Altogether, these results demonstrate that the Ifi204 gene is activated during macrophage development and suggest that the Ifi204 protein may act as a regulator of the balance between proliferation and differentiation. Moreover, this study suggests that other members of the Ifi family might act as regulators of hematopoiesis under the control of hemopoietic cytokines.

Key Words: gene trap • myeloid differentiation • CSF-1 • HIN 200 family




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