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

Amy M. Becker, Drew G. Michael, Ansuman T. Satpathy, Roger Sciammas, Harinder Singh, Deepta Bhattacharya

Research output: Contribution to journalArticle

89 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2003-2012
Number of pages10
JournalBlood
Volume119
Issue number9
DOIs
StatePublished - Mar 1 2012
Externally publishedYes

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Cell Lineage
Dendritic Cells
Neutrophils
Myeloid Progenitor Cells
Granulocyte-Macrophage Progenitor Cells
Macrophages
Microarrays
Blood
Defects

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

IRF-8 extinguishes neutrophil production and promotes dendritic cell lineage commitment in both myeloid and lymphoid mouse progenitors. / Becker, Amy M.; Michael, Drew G.; Satpathy, Ansuman T.; Sciammas, Roger; Singh, Harinder; Bhattacharya, Deepta.

In: Blood, Vol. 119, No. 9, 01.03.2012, p. 2003-2012.

Research output: Contribution to journalArticle

Becker, Amy M. ; Michael, Drew G. ; Satpathy, Ansuman T. ; Sciammas, Roger ; Singh, Harinder ; Bhattacharya, Deepta. / IRF-8 extinguishes neutrophil production and promotes dendritic cell lineage commitment in both myeloid and lymphoid mouse progenitors. In: Blood. 2012 ; Vol. 119, No. 9. pp. 2003-2012.
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