Gimferer, Idoia and Hu, Taishan and Simmons, Amie and Wang, Chi and Souabni, Abdallah and Busslinger, Meinrad and Bender, Timothy P. and Hernandez-Hoyos, Gabriela and Alberola-Ila, José (2011) Regulation of GATA-3 Expression during CD4 Lineage Differentiation. Journal of Immunology, 186 (7). pp. 3892-3898. ISSN 0022-1767 http://resolver.caltech.edu/CaltechAUTHORS:20110411-105608478
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GATA-3 is necessary for the development of MHC class II-restricted CD4 T cells, and its expression is increased during positive selection of these cells. TCR signals drive this upregulation, but the signaling pathways that control this process are not well understood. Using genetic and pharmacological approaches, we show that GATA-3 upregulation during thymocyte-positive selection is the result of additive inputs from the Ras/MAPK and calcineurin pathways. This upregulation requires the presence of the transcription factor c-Myb. Furthermore, we show that TH-POK can also upregulate GATA-3 in double-positive thymocytes, suggesting the existence of a positive feedback loop that contributes to lock in the initial commitment to the CD4 lineage during differentiation.
|Additional Information:||© 2011 American Association of Immunologists, Inc. Received October 22, 2010; Accepted January 20, 2011. Published online before print February 25, 2011. This work was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (Grant AI059302 to J.A.-I.), the American Heart Association (Grant 0855002F to J.A.-I.), and a grant from the Spanish Education and Science Department (to I.G.). We thank Drs. D. Straus, J. Downward, F. Macian, D. Cantrell, A. Weiss, J. Pomerantz, and D. Kappes for providing reagents and animals and S. Kovats (Oklahoma Medical Research Foundation) for discussions.|
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|Deposited By:||Jason Perez|
|Deposited On:||12 Apr 2011 20:27|
|Last Modified:||12 Apr 2011 20:27|
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