HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Matsuda, J. L. Articles by Gapin, L. Search for Related Content PubMed PubMed Citation Articles by Matsuda, J. L. Articles by Gapin, L.

Temporal Dissection of T-bet Functions¹

Jennifer L. Matsuda^*, Thaddeus C. George, James Hagman^* and Laurent Gapin^2,*

^* Integrated Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Science Center, Denver, CO 80206; and Amnis, Seattle, WA 98121

T-bet is a transcription factor of the T-box family that regulates the expression of numerous immune system-associated genes. T-bet directs the acquisition of the Th1-associated genetic program in differentiating CD4⁺ lymphocytes. It also influences the development of NK and NKT cells through its regulation of the IL-2/IL-15R-chain (CD122) and the trafficking of these lymphocytes through CxCR3. The temporal requirements of T-bet activity for the production of IFN- and the regulation of CD122 and CxCR3 expression remain undefined. We produced an ectopically controllable form of T-bet by fusing its C-terminal domain with a mutated ligand-binding domain of human estrogen receptor . By temporally controlling the expression of T-bet-estrogen receptor by the addition or removal of 4-hydroxytamoxifen (4-HT), we show that IFN-, CD122, and CxCR3 are direct gene targets of T-bet whose expression are acutely regulated by T-bet activity.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants R01 AI057485 (to L.G.), P01 AI22295, R01 AI054661, and R01 AI056322 (to J.H.). Support was also provided by a grant from the Cancer League of Colorado (to L.G.) and a postdoctoral fellowship from the American Cancer Society (to J.L.M.).

² Address correspondence and reprint requests to Dr. Laurent Gapin, Integrated Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Science Center, 1400 Jackson Street, Denver, CO 80206. E-mail address: gapinl{at}njc.org

³ Abbreviations used in this paper: 4-HT, 4-hydroxytamoxifen; ER, estrogen receptor ; IRES, internal ribosomal entry sequence; eGFP, enhanced GFP; CHX, cycloheximide; GR, glucocorticoid receptor.

This article has been cited by other articles:

				M. D. Lewis, S. A. Miller, M. M. Miazgowicz, K. M. Beima, and A. S. Weinmann T-bet's Ability To Regulate Individual Target Genes Requires the Conserved T-Box Domain To Recruit Histone Methyltransferase Activity and a Separate Family Member-Specific Transactivation Domain Mol. Cell. Biol., December 15, 2007; 27(24): 8510 - 8521. [Abstract] [Full Text] [PDF]