title: Interferon regulatory factor 8 and the regulation of neutrophil, monocyte, and dendritic cell production.
abstract: OBJECTIVE
  Interferon regulatory factor 8 (IRF8) is a transcription factor that plays central roles in the regulation of myeloid cell fate. In both mice and humans, IRF8 is required for the differentiation of most monocyte and dendritic cell subsets, but suppresses neutrophil production. IRF8 mutations can cause immunodeficiency, and the dysregulated differentiation that underlies myeloid leukemia has been attributed in part to reduced IRF8 expression. In this review we discuss recent studies that have revealed molecular mechanisms underlying the regulation of myelopoiesis by IRF8, which cooperates with other transcription factors to control the initiation of gene expression programs that define the development of specific myeloid cell subsets.
  
  
  RESULTS
  It is now clear that IRF8 regulates cell fate choice by both promoting monocyte/dendritic cell differentiation and suppressing neutrophil differentiation. Recent studies have shown that it collaborates with PU.1 to promote monocyte gene expression (in part via induction of Krüppel-like factor-4), associates with Batf3 to induce CD8α conventional dendritic cell differentiation via autoregulation of its own expression, and restricts neutrophil gene expression by disrupting the binding of c/EBPα to target genes.
  
  
  CONCLUSIONS
  These studies have emphasized the importance of IRF8 in the regulation of myelopoiesis and are revealing novel therapeutic targets.
authors.affiliation: aBoard of Governors Regenerative Medicine Institute bResearch Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center cDavid Geffen School of Medicine at UCLA, Los Angeles, California, USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Yáñez
authors.forename: Helen S
authors.initials: HS
authors.lastname: Goodridge
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006410:Hematopoiesis; D006801:Humans; D050835:Interferon Regulatory Factors / Q000502:physiology*; D000090062:Kruppel-Like Factor 4; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism*; D000099185:Interferon Regulatory Factor-8
chemical_list: D050835:Interferon Regulatory Factors; D000090062:Kruppel-Like Factor 4; D000099185:Interferon Regulatory Factor-8; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse