The Journal of Experimental Medicine
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Published 3 June 2002. doi:10.1084/jem.20020170
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© Rockefeller University Press, 0022-1007/2002/6/1379/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 11, June 3, 2002 1379-1386

Essential and Instructive Roles of GATA Factors in Eosinophil Development

Ryutaro Hirasawa1,5, Ritsuko Shimizu2, Satoru Takahashi3, Mitsujiro Osawa1,6, Shu Takayanagi1, Yuko Kato1, Masafumi Onodera1, Naoko Minegishi4, Masayuki Yamamoto2, Katashi Fukao5, Hideki Taniguchi5, Hiromitsu Nakauchi1,6 and Atsushi Iwama1,6

1 Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, and CREST (JST), Tsukuba, Ibaraki 305-8575, Japan
2 Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, Institute of Basic Medical Sciences
3 Department of Anatomy and Embryology, Institute of Basic Medical Sciences
4 College of Medical Technology and Nursing, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
5 Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
6 Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan

Address correspondence to Atsushi Iwama and Hiromitsu Nakauchi, Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan. Phone: 81-3-5449-5332; Fax: 81-3-5449-5451; E-mail: aiwama{at}ims.u-tokyo.ac.jp or nakauchi{at}ims.u-tokyo.ac.jp

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.

Key Words: GATA-1 • GATA-2 • eosinophil • myeloid cell • allergy


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