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IFN Consensus Sequence Binding Protein (Icsbp) Is Critical for Eosinophil Development¹

Maja Milanovic^2,*, Grzegorz Terszowski^2,, Daniela Struck^2,, Oliver Liesenfeld and Dirk Carstanjen^3,*

^* Leibniz-Forschungsinstitut fuer Molekulare Pharmakologie, Berlin, Germany; Department for Immunology, University of Ulm, Ulm, Germany; and Institute for Microbiology and Hygiene, Charité, Benjamin Franklin University Hospital, Berlin, Germany

IFN consensus sequence binding protein (Icsbp) (IFN response factor-8) is a hematopoietic transcription factor with dual functions in myelopoiesis and immunity. In this study, we report a novel role of Icsbp in regulating the development of eosinophils. Loss of Icsbp in mice leads to a reduction of eosinophils in different tissues. During parasite infection with the nematode Nippostrongylus brasiliensis, Icsbp-deficient mice fail to mount eosinophilia despite a vigorous IL-5 response. Numbers of phenotypically defined eosinophil progenitors are decreased and those progenitors have, on a per-cell basis, reduced eosinophil differentiation potential. The transcription factor Gata1, crucial for eosinophil development, is reduced expressed in committed eosinophil progenitors in wells as mature eosinophils. These findings identify Icsbp as a novel transcription factor critical for the development of the eosinophil lineage.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Deutsche Forschungsgemeinschaft to D.C. (CA 306/1–1) and to G.T. (SFB 497).

² M.M., G.T., and D.S. have contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Dirk Carstanjen, Leibniz-Forschungsinstitut fuer Molekulare Pharmakologie, Krahmer Strasse 6, D-12207 Berlin, Germany. E-mail address: carstanjen{at}fmp-berlin.de

⁴ Abbreviations used in this paper: Icsbp, IFN consensus sequence binding protein; Irf8, IFN response factor-8; GMP, granulocyte-monocyte-progenitor; EoP, eosinophil progenitor; EP, erythroid progenitor; β_c, common β-chain.

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The JI 2008 181: 4431-4432. [Full Text]