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

研究成果: Article

19 引用 (Scopus)

抜粋

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.

元の言語English
ページ(範囲)255-264
ページ数10
ジャーナルExperimental Hematology
36
発行部数3
DOI
出版物ステータスPublished - 2008 3

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

フィンガープリント Homeostatic erythropoiesis by the transcription factor IRF2 through attenuation of type I interferon signaling' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

  • これを引用