Essential and instructive roles of GATA factors in eosinophil development

Ryutaro Hirasawa, Ritsuko Shimizu, Satoru Takahashi, Mitsujiro Osawa, Shu Takayanagi, Yuko Kato, Masafumi Onodera, Naoko Minegishi, Masayuki Yamamoto, Katashi Fukao, Hideki Taniguchi, Hiromitsu Nakauchi, Atsushi Iwama

Research output: Contribution to journalArticlepeer-review

157 Citations (Scopus)

Abstract

GATA transcription factors are major regulators of hematopoietic and immune system. Among GATA factors, GATA-1, GATA-2, and GATA-3 play crucial roles in the development of erythroid cells, hematopoietic stem, and progenitor cells, and T helper type 2 (Th2) cells, respectively. A high level of GATA-1 and GATA-2 expression has been observed in eosinophils, but their roles in eosinophil development remain uncertain both in vitro and in vivo. Here we show that enforced expression of GATA-1 in human primary myeloid progenitor cells completely switches myeloid cell fate into eosinophils. Expression of GATA-1 exclusively promotes development and terminal maturation of eosinophils. Functional domain analyses revealed that the COOH-terminal finger is essential for this capacity while the other domains are dispensable. Importantly, GATA-1-deficient mice failed to develop eosinophil progenitors in the fetal liver. On the other hand, GATA-2 also showed instructive capacity comparable to GATA-1 in vitro and efficiently compensated for GATA-1 deficiency in terms of eosinophil development in vivo, indicating that proper accumulation of GATA factors is critical for eosinophil development. Taken together, our findings establish essential and instructive roles of GATA factors in eosinophil development. GATA-1 and GATA-2 could be novel molecular targets for therapeutic approaches to allergic inflammation.

Original languageEnglish
Pages (from-to)1379-1386
Number of pages8
JournalJournal of Experimental Medicine
Volume195
Issue number11
DOIs
Publication statusPublished - 2002 Jun 3

Keywords

  • Allergy
  • Eosinophil
  • GATA-1
  • GATA-2
  • Myeloid cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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