Homeostatic erythropoiesis by the transcription factor IRF2 through attenuation of type I interferon signaling

Tatsuaki Mizutani, Kohichiro Tsuji, Yasuhiro Ebihara, Shinsuke Taki, Yusuke Ohba, Tadatsugu Taniguchi, Kenya Honda

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Objective: Erythrocyte production is tightly regulated by cytokines, particularly erythropoietin (EPO), which affects expansion and viability of erythroid lineage cells via induction of several factors, including Bcl2-like 1 (Bcl-XL). Because type I interferon (IFN) is known to inhibit erythropoiesis, we studied mice deficient in the gene for interferon regulatory factor 2 (IRF2), which functions as a negative regulator of type I IFN signaling, in the context of erythropoiesis regulation. Materials and Methods: We performed hematologic analyses and detected normocytic anemia in Irf2-deficient mice. Results: Assessment of the maturation of erythroid progenitors in Irf2-deficient bone marrow by flow cytometry revealed a decreased number of late erythroblasts accompanied by an increased number of early erythroid progenitors. Irf2-deficient mice manifested elevated serum EPO levels, decreased Bcl-XL expression levels and enhanced apoptosis of erythroblasts, which may account for the decreased number of late erythroblasts. We further assessed the role of IRF2 in the regulation of type I IFN signaling during erythropoiesis, and found that additional homozygous mutation of IFNAR1, a subunit of type I IFN receptor complex, led to rescue of the defect of erythropoiesis in Irf2-deficient mice. Conclusions: Impaired erythropoiesis in Irf2-deficient mice results from excessive type I IFN signaling, which inhibits Bcl-XL expression in erythroid lineage cells. Our present study provides a mechanistic understanding of the potential cross-talk between type I IFN and EPO signaling pathways during erythropoiesis and may offer therapeutic insights into anemia.

Original languageEnglish
Pages (from-to)255-264
Number of pages10
JournalExperimental Hematology
Volume36
Issue number3
DOIs
Publication statusPublished - 2008 Mar
Externally publishedYes

Fingerprint

Interferon Regulatory Factor-2
Interferon Type I
Erythropoiesis
Transcription Factors
Erythroblasts
Erythropoietin
Erythroid Cells
Anemia
Interferon alpha-beta Receptor
Flow Cytometry
Erythrocytes
Bone Marrow
Apoptosis
Cytokines
Mutation

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

Homeostatic erythropoiesis by the transcription factor IRF2 through attenuation of type I interferon signaling. / Mizutani, Tatsuaki; Tsuji, Kohichiro; Ebihara, Yasuhiro; Taki, Shinsuke; Ohba, Yusuke; Taniguchi, Tadatsugu; Honda, Kenya.

In: Experimental Hematology, Vol. 36, No. 3, 03.2008, p. 255-264.

Research output: Contribution to journalArticle

Mizutani, Tatsuaki ; Tsuji, Kohichiro ; Ebihara, Yasuhiro ; Taki, Shinsuke ; Ohba, Yusuke ; Taniguchi, Tadatsugu ; Honda, Kenya. / Homeostatic erythropoiesis by the transcription factor IRF2 through attenuation of type I interferon signaling. In: Experimental Hematology. 2008 ; Vol. 36, No. 3. pp. 255-264.
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