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International Immunology Advance Access originally published online on May 10, 2004
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International Immunology, Vol. 16, No. 6, pp. 867-875, June 2004
© 2004 Japanese Society for Immunology

Proteins of the Ikaros family control dendritic cell maturation required to induce optimal Th1 T cell differentiation

Mojgan Movassagh, Diego Laderach and Anne Galy1

Barbara Ann Karmanos Cancer Institute and Department of Immunology and Microbiology, Wayne State University, Detroit, MI 48201 USA 1 INSERM U362, Institut Gustave Roussy, Villejuif and Généthon, Evry, France

Correspondence to: A. Galy; E-mail: galy{at}genethon.fr
Transmitting editor: G. Trinchieri

Ikaros proteins are pleiotropic regulators of hematopoiesis and are critically required for the production of lymphocyte and dendritic cell (DC) lineages in mice. Here, we asked if Ikaros proteins could also play a role in the late stages of dendritic cell differentiation. Nuclear Ikaros proteins were up-regulated during the in vitro differentiation of human monocytes into mature DC, suggesting potential implications in this process. To address this question, a dominant negative mutant Ikaros isoform IK7 was over-expressed by retroviral gene transfer in human DC precursor cells, to interfere with the function of Ikaros family members during DC development. Expression of IK7 in CD34+ cells inhibited the production of IL-12-producing APCs. The resulting progeny of CD34+ cells and in particular, committed CD1a+ DC or CD14+ cell-derived DC, expressed low levels of MHC class II antigens and of the CD83 maturation marker on the cell surface. Such IK7-expressing DC induced naïve allogeneic T cells to produce Th2 cytokines. Our results therefore delineate a new role for Ikaros family members, showing that normal levels of Ikaros proteins are essential in DC to regulate the terminal stages of maturation and the capacity to induce optimal Th1 T cell responses.

Keywords: antigen presentation, dendritic cells, human, transcription factors


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