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United States Department of Agriculture

Agricultural Research Service

Research Project: DIET AND IMMUNE FUNCTION RELATED TO INFECTIOUS AND ALLERGIC DISEASE

Location: Diet, Genomics and Immunology Lab

Title: The transcription factor GATA3 actively represses RUNX3 protein-regulated production of interferon-gamma

Authors
item Yagi, Ryoji -
item Junttila, Ilkka -
item Wei, Gang -
item Urban, Joseph
item Zhao, Keji -
item Paul, William -
item Zhu, Jinfang -

Submitted to: Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 15, 2010
Publication Date: April 23, 2010
Citation: Yagi, R., Junttila, I., Wei, G., Urban Jr, J.F., Zhao, K., Paul, W., Zhu, J. 2010. The transcription factor GATA3 actively represses RUNX3 protein-regulated production of interferon-gamma. Immunity. 32:507-517.

Interpretive Summary: Given that more than one third of the world’s population is infected with gastrointestinal roundworms (worms) and that the response to a worm infection is similar to that caused by allergens, it is important to understand the mechanisms that control these responses. The current study demonstrates that induction of an allergic response activates suppression of proteins that control responses to certain pathogens like certain bacteria, viruses, and protozoan parasites. Knowledge of how these are suppressed will help develop strategies to ensure that protective immune responses to pathogens can remain active and functional during times of worm infection or during allergic responses to food and environmental allergens. This work is important to the progress of research to control allergic disease and the mechanisms that regulate efficient immune function, and to scientists that determine ways to regulate these responses.

Technical Abstract: The transcription factor GATA3 is crucial for the differentiation of naive CD4+ T cells into T helper 2 (Th2) cells. Here, we show that deletion of Gata3 allowed the appearance of interferon-g (IFN-g)-producing cells in the absence of interleukin-12 (IL-12) and IFN-g. Such IFN-g production was transcription factor T-bet independent. Another T-box-containing transcription factor, Eomes, but not T-bet, was induced both in GATA3-deficient CD4+ T cells differentiated under Th2 cell conditions and in Th2 cells with enforced Runx3 expression, contributing to IFN-g production. GATA3 over-expression blocked Runx3-mediated Eomes induction and IFN-g production, and GATA3 protein physically interacted with Runx3 protein. Furthermore, we found that Runx3 bound directly to multiple regulatory elements of the IFN-g gene and that blocking Runx3 function in either Th1 or GATA3-deficient ‘‘Th2’’ cells resulted in diminished IFN-g production by these cells. Thus, the Runx3-mediated pathway, actively suppressed by GATA3, induces IFN-g production in a STAT4- and T-bet-independent manner.

Last Modified: 4/21/2014
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