Cutting edge: IRF8 regulates Bax transcription in vivo in primary myeloid cells

A prominent phenotype of IRF8 knockout (KO) mice is the uncontrolled expansion of immature myeloid cells. The molecular mechanism underlying this myeloproliferative syndrome is still elusive. In this study, we observed that Bax expression level is low in bone marrow preginitor cells and increases dr...

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Published inThe Journal of immunology (1950) Vol. 187; no. 9; pp. 4426 - 4430
Main Authors Yang, Jine, Hu, Xiaolin, Zimmerman, Mary, Torres, Christina M, Yang, Dafeng, Smith, Sylvia B, Liu, Kebin
Format Journal Article
LanguageEnglish
Published United States 01.11.2011
Subjects
Animals
Apoptosis - immunology
bcl-2-Associated X Protein - genetics
bcl-2-Associated X Protein - metabolism
Cell Differentiation - genetics
Cell Differentiation - immunology
Cell Lineage - immunology
Interferon Regulatory Factors - metabolism
Interferon Regulatory Factors - physiology
Mice
Mice, Inbred C57BL
Mice, Knockout
Myeloid Cells - cytology
Myeloid Cells - immunology
Myeloid Cells - metabolism
Primary Cell Culture
Promoter Regions, Genetic - immunology
Protein Binding - genetics
Protein Binding - immunology
Splenomegaly - immunology
Splenomegaly - metabolism
Splenomegaly - pathology
Transcription, Genetic - immunology
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Summary:A prominent phenotype of IRF8 knockout (KO) mice is the uncontrolled expansion of immature myeloid cells. The molecular mechanism underlying this myeloproliferative syndrome is still elusive. In this study, we observed that Bax expression level is low in bone marrow preginitor cells and increases dramatically in primary myeloid cells in wt mice. In contrast, Bax expression level remained at a low level in primarymyeloid cells in IRF8 KO mice. However, in vitro IRF8 KO bone marrow-differentiated myeloid cells expressed Bax at a level as high as that in wild type myeloid cells. Furthermore, we demonstrated that IRF8 specifically binds to the Bax promoter region in primary myeloid cells. Functional analysis indicated that IRF8 deficiency results in increased resistance of the primary myeloid cells to Fas-mediated apoptosis. Our findings show that IRF8 directly regulates Bax transcription in vivo, but not in vitro during myeloid cell lineage differentiation.
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ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1101034