The Journal of Experimental Medicine
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Published 22 February 2005. doi:10.1084/jem.20041330
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 4, 615-626
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ARTICLE

 Ets-1, a functional cofactor of T-bet, is essential for Th1 inflammatory responses

Roland Grenningloh1, Bok Yun Kang1, and I-Cheng Ho1,2

1 Department of Medicine, Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA 02115
2 Harvard Medical School, Boston, MA 02115

CORRESPONDENCE I-Cheng Ho: iho{at}partners.org

To mount an effective type 1 immune response, type 1 T helper (Th1) cells must produce inflammatory cytokines and simultaneously suppress the expression of antiinflammatory cytokines. How these two processes are coordinately regulated at the molecular level is still unclear. In this paper, we show that the proto-oncogene E26 transformation–specific-1 (Ets-1) is necessary for T-bet to promote interferon-{gamma} production and that Ets-1 is essential for mounting effective Th1 inflammatory responses in vivo. In addition, Ets-1–deficient Th1 cells also produce a very high level of interleukin 10. Thus, Ets-1 plays a crucial and unique role in the reciprocal regulation of inflammatory and antiinflammatory Th responses.

Abbreviations used: ChIP, chromatin immunoprecipitation; Ets-1, E26 transformation–specific-1; ICS, intracellular cytokine staining; ISRE, IFN-stimulated response element.


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