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CUTTING EDGE |
*
Department of Pathology and Center for Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110;
Department of Immunology, University of California, Berkeley, CA 94720; and
Roche Bioscience, Palo Alto, CA 94303
Previously, we analyzed the proximal IL-4 promoter in directing Th2-specific activity. An 800-base pair proximal promoter conferred some Th2-selective expression in transgenic mice. However, this region directed extremely low reporter mRNA levels relative to endogenous IL-4 mRNA, suggesting that full gene activity requires additional enhancer elements. Here, we analyzed large genomic IL-4 regions for enhancer activity and interaction with transcription factors. The proximal IL-4 promoter is only moderately augmented by GATA-3, but certain genomic regions significantly enhanced GATA-3 promoter transactivation. Some enhancing regions contained consensus GATA sites that bound Th2-specific complexes. However, retroviral transduction of GATA-3 into developing T cells induced IL-5 to full Th2 levels, but only partially restored IL-4 production. Thus, we propose that GATA-3 is permissive, but not sufficient, for full IL-4 enhancement and may act through GATA elements surrounding the IL-13/IL-4 gene locus.
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D. Bhattacharya, D. U. Lee, and W. C. Sha Regulation of Ig class switch recombination by NF-{kappa}B: retroviral expression of RelB in activated B cells inhibits switching to IgG1, but not to IgE Int. Immunol., September 1, 2002; 14(9): 983 - 991. [Abstract] [Full Text] [PDF]
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H. Kurata, H.-J. Lee, T. McClanahan, R. L. Coffman, A. O'Garra, and N. Arai Friend of GATA Is Expressed in Naive Th Cells and Functions As a Repressor of GATA-3-Mediated Th2 Cell Development J. Immunol., May 1, 2002; 168(9): 4538 - 4545. [Abstract] [Full Text] [PDF]
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J. P. Justice, M. T. Borchers, J. J. Lee, W. H. Rowan, Y. Shibata, and M. R. Van Scott Ragweed-induced expression of GATA-3, IL-4, and IL-5 by eosinophils in the lungs of allergic C57BL/6J mice Am J Physiol Lung Cell Mol Physiol, February 1, 2002; 282(2): L302 - L309. [Abstract] [Full Text] [PDF]
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G. T. F. Schwenger, R. Fournier, C. C. Kok, V. A. Mordvinov, D. Yeoman, and C. J. Sanderson GATA-3 Has Dual Regulatory Functions in Human Interleukin-5 Transcription J. Biol. Chem., December 14, 2001; 276(51): 48502 - 48509. [Abstract] [Full Text] [PDF]
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M. Zhou, W. Ouyang, Q. Gong, S. G. Katz, J. M. White, S. H. Orkin, and K. M. Murphy Friend of GATA-1 Represses GATA-3-dependent Activity in CD4+ T Cells J. Exp. Med., November 12, 2001; 194(10): 1461 - 1471. [Abstract] [Full Text] [PDF]
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A. Wensky, M. C. Garibaldi Marcondes, and J. J. Lafaille The Role of IFN-{gamma} in the Production of Th2 Subpopulations: Implications for Variable Th2-Mediated Pathologies in Autoimmunity J. Immunol., September 15, 2001; 167(6): 3074 - 3081. [Abstract] [Full Text] [PDF]
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M. C. Nawijn, G. M. Dingjan, R. Ferreira, B. N. Lambrecht, A. Karis, F. Grosveld, H. Savelkoul, and R. W. Hendriks Enforced Expression of GATA-3 in Transgenic Mice Inhibits Th1 Differentiation and Induces the Formation of a T1/ST2-Expressing Th2-Committed T Cell Compartment In Vivo J. Immunol., July 15, 2001; 167(2): 724 - 732. [Abstract] [Full Text] [PDF]
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H. Zhu, J. Yang, T. L. Murphy, W. Ouyang, F. Wagner, A. Saparov, C. T. Weaver, and K. M. Murphy Unexpected Characteristics of the IFN-{{gamma}} Reporters in Nontransformed T Cells J. Immunol., July 15, 2001; 167(2): 855 - 865. [Abstract] [Full Text] [PDF]
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J. J. Wallin, L. Liang, A. Bakardjiev, and W. C. Sha Enhancement of CD8+ T Cell Responses by ICOS/B7h Costimulation J. Immunol., July 1, 2001; 167(1): 132 - 139. [Abstract] [Full Text] [PDF]
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S. Finotto, G. T. De Sanctis, H. A. Lehr, U. Herz, M. Buerke, M. Schipp, B. Bartsch, R. Atreya, E. Schmitt, P. R. Galle, et al. Treatment of Allergic Airway Inflammation and Hyperresponsiveness by Antisense-Induced Local Blockade of Gata-3 Expression J. Exp. Med., June 4, 2001; 193(11): 1247 - 1260. [Abstract] [Full Text] [PDF]
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J. S. Burr, N. D. L. Savage, G. E. Messah, S. L. Kimzey, A. S. Shaw, R. H. Arch, and J. M. Green Cutting Edge: Distinct Motifs Within CD28 Regulate T Cell Proliferation and Induction of Bcl-XL J. Immunol., May 1, 2001; 166(9): 5331 - 5335. [Abstract] [Full Text] [PDF]
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S. Ranganath and K. M. Murphy Structure and Specificity of GATA Proteins in Th2 Development Mol. Cell. Biol., April 15, 2001; 21(8): 2716 - 2725. [Abstract] [Full Text]
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J. D. Farrar, W. Ouyang, M. Lohning, M. Assenmacher, A. Radbruch, O. Kanagawa, and K. M. Murphy An Instructive Component in T Helper Cell Type 2 (Th2) Development Mediated by Gata-3 J. Exp. Med., March 5, 2001; 193(5): 643 - 650. [Abstract] [Full Text] [PDF]
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N. Takemoto, Y. Kamogawa, H. Jun Lee, H. Kurata, K.-i. Arai, A. O'Garra, N. Arai, and S. Miyatake Cutting Edge: Chromatin Remodeling at the IL-4/IL-13 Intergenic Regulatory Region for Th2-Specific Cytokine Gene Cluster J. Immunol., December 15, 2000; 165(12): 6687 - 6691. [Abstract] [Full Text] [PDF]
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C.-H. Chen, D.-H. Zhang, J. M. LaPorte, and A. Ray Cyclic AMP Activates p38 Mitogen-Activated Protein Kinase in Th2 Cells: Phosphorylation of GATA-3 and Stimulation of Th2 Cytokine Gene Expression J. Immunol., November 15, 2000; 165(10): 5597 - 5605. [Abstract] [Full Text] [PDF]
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T. L. Murphy, E. D. Geissal, J. D. Farrar, and K. M. Murphy Role of the Stat4 N Domain in Receptor Proximal Tyrosine Phosphorylation Mol. Cell. Biol., October 1, 2000; 20(19): 7121 - 7131. [Abstract] [Full Text]
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H. J. Lee, N. Takemoto, H. Kurata, Y. Kamogawa, S. Miyatake, A. O'Garra, and N. Arai Gata-3 Induces T Helper Cell Type 2 (Th2) Cytokine Expression and Chromatin Remodeling in Committed Th1 Cells J. Exp. Med., July 3, 2000; 192(1): 105 - 116. [Abstract] [Full Text] [PDF]
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J. D. Farrar, J. D. Smith, T. L. Murphy, and K. M. Murphy Recruitment of Stat4 to the Human Interferon-alpha /beta Receptor Requires Activated Stat2 J. Biol. Chem., January 28, 2000; 275(4): 2693 - 2697. [Abstract] [Full Text] [PDF]
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R. Chen, T. F. Burke, J. E. Cumberland, M. Brummet, L. A. Beck, V. Casolaro, and S. N. Georas Glucocorticoids Inhibit Calcium- and Calcineurin-Dependent Activation of the Human IL-4 Promoter J. Immunol., January 15, 2000; 164(2): 825 - 832. [Abstract] [Full Text] [PDF]
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 D. A. Randolph, G. Huang, C. J. Carruthers, L. E. Bromley, and D. D. Chaplin The Role of CCR7 in TH1 and TH2 Cell Localization and Delivery of B Cell Help in Vivo Science, December 10, 1999; 286(5447): 2159 - 2162. [Abstract] [Full Text]
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W. Ouyang, N. G. Jacobson, D. Bhattacharya, J. D. Gorham, D. Fenoglio, W. C. Sha, T. L. Murphy, and K. M. Murphy The Ets transcription factor ERM is Th1-specific and induced by IL-12 through a Stat4-dependent pathway PNAS, March 30, 1999; 96(7): 3888 - 3893. [Abstract] [Full Text] [PDF]
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 R.A. FLAVELL, B. LI, C. DONG, H.-T. LU, D. D. YANG, H. ENSLEN, C. TOURNIER, A. WHITMARSH, M. WYSK, D. CONZE, et al. Molecular Basis of T-cell Differentiation Cold Spring Harb Symp Quant Biol, January 1, 1999; 64(0): 563 - 572. [Abstract] [PDF]
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K.M. MURPHY, W. OUYANG, S. RANGANATH, and T.L. MURPHY Bi-stable Transcriptional Circuitry and GATA-3 Auto-activation in Th2 Commitment Cold Spring Harb Symp Quant Biol, January 1, 1999; 64(0): 585 - 588. [Abstract] [PDF]
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N. ARAI, H.J. LEE, I. FERBER, H. KURATA, and A. O'GARRA Multiple Levels of Regulation of Th2 Cytokine Gene Expression Cold Spring Harb Symp Quant Biol, January 1, 1999; 64(0): 589 - 598. [Abstract] [PDF]
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