Published 12 November 2001. doi:10.1084/jem.194.10.1461
© Rockefeller University Press, 0022-1007/2001/11/1461/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 10, November 19, 2001 1461-1471
Friend of GATA-1 Represses GATA-3dependent Activity in CD4+ T Cells
Meixia Zhou1,
Wenjun Ouyang1,
Qian Gong2,
Samuel G. Katz3,
J. Michael White1,
Stuart H. Orkin3 and
Kenneth M. Murphy1
1 Department of Pathology and Immunology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110
2 Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110
3 Division of Hematology/Oncology, The Children's Hospital Medical Center, and Dana Farber Cancer Institute, Department of Pediatrics, Harvard Medical School, Howard Hughes Medical Institute, Boston, MA 02115
Address correspondence to Kenneth M. Murphy, Dept. of Pathology and Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110. Phone: 314-362-2009; Fax: 314-747-4888; E-mail: Murphy{at}immunology.wustl.edu
The development of naive CD4+ T cells into a T helper (Th) 2 subset capable of producing interleukin (IL)-4, IL-5, and IL-13 involves a signal transducer and activator of transcription (Stat)6-dependent induction of GATA-3 expression, followed by Stat6-independent GATA-3 autoactivation. The friend of GATA (FOG)-1 protein regulates GATA transcription factor activity in several stages of hematopoietic development including erythrocyte and megakaryocyte differentiation, but whether FOG-1 regulates GATA-3 in T cells is uncertain. We show that FOG-1 can repress GATA-3dependent activation of the IL-5 promoter in T cells. Also, FOG-1 overexpression during primary activation of naive T cells inhibited Th2 development in CD4+ T cells. FOG-1 fully repressed GATA-3dependent Th2 development and GATA-3 autoactivation, but not Stat6-dependent induction of GATA-3. FOG-1 overexpression repressed development of Th2 cells from naive T cells, but did not reverse the phenotype of fully committed Th2 cells. Thus, FOG-1 may be one factor capable of regulating the Th2 development.
Key Words: GATA-3 FOG-1 thymocyte T lymphocyte cytokine

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