NDLI: IRF-8 extinguishes neutrophil production and promotes dendritic cell lineage commitment in both myeloid and lymphoid mouse progenitors

Content Provider	PubMed Central
Author	Becker, Amy M. Michael, Drew G. Satpathy, Ansuman T. Roger, Sciammas Singh, Harinder Bhattacharya, Deepta
Copyright Year	2012
Abstract	While most blood lineages are assumed to mature through a single cellular and developmental route downstream of HSCs, dendritic cells (DCs) can be derived from both myeloid and lymphoid progenitors in vivo. To determine how distinct progenitors can generate similar downstream lineages, we examined the transcriptional changes that accompany loss of in vivo myeloid potential as common myeloid progenitors differentiate into common DC progenitors (CDPs), and as lymphoid-primed multipotent progenitors (LMPPs) differentiate into all lymphoid progenitors (ALPs). Microarray studies revealed that IFN regulatory factor 8 (IRF-8) expression increased during each of these transitions. Competitive reconstitutions using Irf8 −/− BM demonstrated cell-intrinsic defects in the formation of CDPs and all splenic DC subsets. Irf8 −/− common myeloid progenitors and, unexpectedly, Irf8 −/− ALPs produced more neutrophils in vivo than their wild-type counterparts at the expense of DCs. Retroviral expression of IRF-8 in multiple progenitors led to reduced neutrophil production and increased numbers of DCs, even in the granulocyte-macrophage progenitor (GMP), which does not normally possess conventional DC potential. These data suggest that IRF-8 represses a neutrophil module of development and promotes convergent DC development from multiple lymphoid and myeloid progenitors autonomously of cellular context.
Related Links	http://dx.doi.org/10.1182/blood-2011-06-364976
Ending Page	2012
Page Count	10
Starting Page	2003
File Format	PDF
ISSN	00064971
e-ISSN	15280020
Journal	Blood
Issue Number	9
Volume Number	119
Language	English
Publisher	American Society of Hematology
Publisher Date	2012-03-01
Access Restriction	Open
Rights Holder	American Society of Hematology
Subject Keyword	Immunology Cell Biology Biochemistry Hematology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Hematology Biochemistry Immunology

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