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

• Published in: The Journal of immunology (1950) Vol. 181; no. 7; pp. 5045 - 5053
• Main Authors: Milanovic, Maja, Terszowski, Grzegorz, Struck, Daniela, Liesenfeld, Oliver, Carstanjen, Dirk
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.10.2008
• Subjects: Animals; Cell Differentiation - genetics; Cell Differentiation - immunology; Cells, Cultured; Consensus Sequence - genetics; Consensus Sequence - immunology; Eosinophilia - genetics; Eosinophilia - immunology; Eosinophilia - parasitology; Eosinophils - immunology; Eosinophils - metabolism; Eosinophils - parasitology; Eosinophils - pathology; Interferon Regulatory Factors - deficiency; Interferon Regulatory Factors - genetics; Interferon Regulatory Factors - physiology; Leukocyte Count; Mice; Mice, Inbred C57BL; Mice, Knockout; Nippostrongylus - immunology; Rats; Rats, Inbred Lew; Strongylida Infections - genetics; Strongylida Infections - immunology; Strongylida Infections - pathology; Transcription, Genetic - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.181.7.5045

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.