Immunologic Research

, Volume 28, Issue 1, pp 25–37 | Cite as

The function role of GATA-3 in Th1 and Th2 differentiation

  • Meixia Zhou
  • Wenjun Ouyang


GATA-3 plays a central role in regulating Th1 and Th2 cell differentiation. Upon interleukin (IL)-4 binding to its receptor, GATA-3 is induced through the action of Stat6. GATA-3 regulates Th2 cytokine expression notonly at the transcription level, such asdirectly binding to the promoters of the IL-5 and IL-13 gene, but also by the involvement in the remodeling of the chromatin structure and opening the IL-4 locus. As a master control, GATA-3 stabilizes the Th2 phenotype by two methods. First, GATA-3 shuts down Th1 development through the repression the IL-12 receptor β2-chain expression. Second, GATA-3 augments its own expression by a positive feedback autoregulation. In this article, we review the recent study of the function of GATA-3 in Th1 and Th2 differentiation.

Key Words

Th1 Th2 GATA-3 Cytokines IFN-γ IL-4 Transcription factors 


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  1. 1.
    Mosmann TR, Cherwinski H, Bond HW, Giedlin MA, Coffman RL: Two types of murine helper T cell clone. I. Definition accordingto profiles of lymphokineactivities and secreted proteins. J Immunol 1986;136:2348–2357.PubMedGoogle Scholar
  2. 2.
    Stenger S, Thuring H, Rollinghoff M, Bogdan C: Tissue expression of inducible nitric oxide synthase is closely associated with resistance to Leishmania major. J Exp Med 1994;180(3):783–793.PubMedCrossRefGoogle Scholar
  3. 3.
    Reiner SL, Seder RA: T helper cell differentiation in immune response. Curr Opin Immunol 1995;7(3):360–366.PubMedCrossRefGoogle Scholar
  4. 4.
    Farrar MA, Schreiber RD: Themolecular cell biology of interferon-gamma and its receptor. Annu Rev Immunol 1993;11:571–611.PubMedCrossRefGoogle Scholar
  5. 5.
    Robinson DS, Hamid Q, Ying S, Tsicopoulos A, Barkans J, Bentley AM, et al.: Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med 1992;326(5):298–304.PubMedCrossRefGoogle Scholar
  6. 6.
    Erb KJ, Le Gros G: The role of Th2 type CD4+ T cells and Th2 type CD8+ T cells in asthma. Immunol Cell Biol 1996;74(2):206–208.PubMedGoogle Scholar
  7. 7.
    Kopf M, LeGros G, Bachmann M, Lamers MC, Bluethmann H, Kohler G: Disruption of the murine IL-4 gene blocks Th2 cytokine responses. Nature 1993;362(6417): 245–248.PubMedCrossRefGoogle Scholar
  8. 8.
    Kuhn R, Rajewsky K, Muller W: Generation and analysis of interleukin-4 deficient mice. Science 1991;254(5032):707–710.PubMedCrossRefGoogle Scholar
  9. 9.
    Abbas AK, Murphy KM, Sher A: Functional diversity of helper T lymphocytes. Nature 1996;383 (6603):787–793.PubMedCrossRefGoogle Scholar
  10. 10.
    Seder RA, Paul WE: Acquisition of lymphokine-producing phenotype by CD4+ T cells. Annu Rev Immunol 1994;12:635–673.PubMedCrossRefGoogle Scholar
  11. 11.
    Mosley B, Beckmann MP, March CJ, Idzerda RL, Gimpel SD, VandenBos T, et al.: The murine interleukin-4 receptor: molecular cloning and characterization of secreted and membrane bound forms. Cell 1989;59(2):335–348.PubMedCrossRefGoogle Scholar
  12. 12.
    Miyazaki T, Kawahara A, Fujii H, Nakagawa Y, Minami Y, Liu ZJ, et al.: Functional activation of Jakl and Jak3 by selective association with IL-2 receptor subunits. Science 1994;266(5187):1045–1047.PubMedCrossRefGoogle Scholar
  13. 13.
    Yin T, Tsang ML, Yang YC: JAK1 kinase forms complexes with interleukin-4 receptor and 4PS/insulin receptor substrate-1-like protein and is activated by interleukin-4 and interleukin-9 in T lymphocytes. J Biol Chem 1994;269(43): 26,614–26,617.Google Scholar
  14. 14.
    Hou J, Schindler U, Henzel WJ, Ho TC, Brasseur M, McKnight SL: An interleukin-4-induced transcription factor: IL-4 Stat. Science 1994;265(5179):1701–1706.PubMedCrossRefGoogle Scholar
  15. 15.
    Quelle FW, Shimoda K, Thierfelder W, Fischer C, Kim A, Ruben SM, et al.: Cloning of murine Stat6 and human Stato, Stat proteins that are tyrosine phosphorylated in responses to IL-4 and IL-3 but are not required for mitogenesis. Mol Cell Biol 1995;15(6):3336–3343.PubMedGoogle Scholar
  16. 16.
    Shimoda K, van Deursen J, Sangster MY, Sarawar SR, Carson RT, Tripp RA, et al.: Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted Stato gene. Nature 1996; 380(6575):630–633.PubMedCrossRefGoogle Scholar
  17. 17.
    Takeda K, Kamanaka M, Tanaka T, Kishimoto T, Akira S: Impaired IL-13-mediated functions of macrophages in STATO-deficient mice. J Immunol 1996;157(8): 3220–3222.PubMedGoogle Scholar
  18. 18.
    Orkin SH: Hematopoiesis: how does it happen? Curr Opin Cell Biol 1995;7(6):870–877.PubMedCrossRefGoogle Scholar
  19. 19.
    Pandolfi PP, Roth ME, Karis A, Leonard MW, Dzierzak E, Grosveld FG, et al.: Targeted disruption of the GATA3 gene causes severe abnormalities in the nervous system and in fetal liver haematopoiesis. Nat Genet 1995; 11:40–44.PubMedCrossRefGoogle Scholar
  20. 20.
    Ting CN, Olson MC, Barton KP, Leiden JM. Transcription factor GATA-3 is required for development of the T-cell lineage. Nature 1996;384:474–478.PubMedCrossRefGoogle Scholar
  21. 21.
    Zheng W, Flavell RA: The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell 1997;89:587–596.PubMedCrossRefGoogle Scholar
  22. 22.
    Siegel MD, Zhang DH, Ray P, Ray A: Activation of the interleukin-5 promoter by cAMP in murine EL-4 cells requires the GATA-3 and CLE elements. J Biol Chem 1995;270(41):24,548–24,555.Google Scholar
  23. 23.
    Zhang DH, Cohn L, Ray P, Bottomly K, Ray A: Transcription factor GATA-3 is differentially expressed in murine Th1 and Th2 cells and controls Th2-specific expression of the interleukin-5 gene. J Biol Chem 1997;272:21,597–21,603.Google Scholar
  24. 24.
    Ouyang W, Ranganath SH, Weindel K, Bhattacharya D, Murphy TL, Sha W, et al.: Inhibition of Th1 development mediated by GATA-3 throughan IL-4-independent mechanism. Immunity 1998;9:745–755.PubMedCrossRefGoogle Scholar
  25. 25.
    Ouyang W, Lohning M, Gao M, Assenmacher M, Ranganath M, Radbruch A, et al.: Stat6-independent GATA-3 autoactivation directs IL-4-independent Th2 development and commitment. Immunity 2000;12:27–37.PubMedCrossRefGoogle Scholar
  26. 26.
    Li-Weber M, Davydov IV, Krafft H, Krammer PH: The role of NF-Y and IRF-2 in the regulation of human IL-4 gene expression. J Immunol 1994;153:4122–4133.PubMedGoogle Scholar
  27. 27.
    Szabo SJ, Gold JS, Murphy TL, Murphy KM: Identification of cis-acting regulatory elements controlling interleukin-4 gene expression in T cells: roles for NF-Y and NF-ATc [published erratum appears in Mol Cell Biol 1993; 13(9):5928]. Mol Cell Biol 1993; 13:4793–4805.PubMedGoogle Scholar
  28. 28.
    Rooney JW, Hoey T, Glimcher LH: Coordinate and cooperative roles for NF-AT and AP-1 in the regulation of the murine IL-4 gene. Immunity 1995;2:473–483.PubMedCrossRefGoogle Scholar
  29. 29.
    Murphy KM, Ouyang W, Farrar JD, Yang J, Ranganath S, Asnagli H, et al.: Signaling and transcription in T helper development. Annu Rev Immunol 2000;18:451–494.PubMedCrossRefGoogle Scholar
  30. 30.
    Wenner CA, Szabo SJ, Murphy KM: Identification of IL-4 promoter elements conferring Th2-restricted expression during T helper cell subset development. J Immunol 1997;158:765–773.PubMedGoogle Scholar
  31. 31.
    Ranganath S, Ouyang W, Bhattarcharya D, Sha WC, Grupe A, Peltz G, et al.: GATA-3-dependent enhancer activity in IL-4 gene regulation. J Immunol 1998;161: 3822–3826.PubMedGoogle Scholar
  32. 32.
    Zhang DH, Yang L, Ray A: Differential responsiveness of the IL-5 and IL-4 genes to transcription factor GATA-3. J Immunol 1998;161:3817–3821.PubMedGoogle Scholar
  33. 33.
    Agarwal S, Rao A: Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation. Immunity 1998;9:765–775.PubMedCrossRefGoogle Scholar
  34. 34.
    Lee HU, Takemoto N, Kurata H, Kamogawa Y, Miyatake S, O'Garra A, et al.: GATA-3 induces T helper cell type 2 (Th2) cytokine expression and chromatin remodeling in committed Th1 cells. J Exp Med 2000;192(1):105–115.PubMedCrossRefGoogle Scholar
  35. 35.
    Takemoto N, Kamogawa Y, Jun Lee H, Kurata H, Arai KI, O'Garra A, et al.: Chromatin remodeling at the IL-4/IL-13 intergenic regulatory region for Th2-specific cytokine gene cluster. J Immunol 2000;165:6687–6691.PubMedGoogle Scholar
  36. 36.
    Loots GG, Locksley RM, Blankespoor CM, Wang ZE, Miller W, Rubin EM, et al.: Identification of a coordinate regulator of interleukins4, 13, and 5 by cross-species sequence comparisons. Science 2000;288(5463):136–140.PubMedCrossRefGoogle Scholar
  37. 37.
    Lee GR, Fields PE, Flavell RA: Regulation of IL-4 gene expression by distal regulatory elements and GATA-3 at the chromatin level. Immunity 2001;14(4):447–459.PubMedCrossRefGoogle Scholar
  38. 38.
    Schwenger GT, Fournier R, Kok CC, Mordvinoy VA, Yeoman D, Sanderson CJ: GATA-3 has dual regulatory functions in human interleukin-5 transcription. J Biol Chem 2001;276(51):48,502–48,509.Google Scholar
  39. 39.
    Defrance T, Carayon P, Billian G, Guillemot JC, Minty A, Caput D, et al.: Interleukin 13 is a B cell stimulating factor. J Exp Med 1994; 179(1):135–143.PubMedCrossRefGoogle Scholar
  40. 40.
    Emson CL, Bell SE, Jones A, Wisden W, McKenzie AN: Interleukin (IL)-4-independent induction of immunoglobulin (Ig)E, and perturbation of T cell development in transgenic mice expressing IL-13. J Exp Med 1998;188(2):399–404.PubMedCrossRefGoogle Scholar
  41. 41.
    Kishikawa H, Sun J, Choi A, Miaw SC, Ho IC: The cell type-specific expression of the murine IL-13 gene is regulated by GATA-3. J Immunol 2001;167(8): 4414–4420.PubMedGoogle Scholar
  42. 42.
    Rao A, Luo C, Hogan PG: Transcription factors of the NFAT family: regulation and function. Annu Rev Immunol 1997;15:707–747.PubMedCrossRefGoogle Scholar
  43. 43.
    Agarwal S, Avni O, Rao A: Cell-type-restricted binding of the transcription factor NFAT to a distal IL-4 enhancer in vivo. Immunity 2000;12(6):643–652.PubMedCrossRefGoogle Scholar
  44. 44.
    Glimcher LH, Singh H: Transcription factors in lymphocyte development—T and B cells get together. Cell 1999;96:13–23.PubMedCrossRefGoogle Scholar
  45. 45.
    Ranger AM, Hodge MR, Gravallese EM, Oukka M, Davidson L, Alt FW, et al.: Delayed lymphoid repopulation with defects in IL-4-driven responses produced by inactivation of NF-ATc. Immunity 1998;8:125–134.PubMedCrossRefGoogle Scholar
  46. 46.
    Yoshida H, Nishina H, Takimoto H, Marengere LE, Wakeham AC, Bouchard D, et al.: The transcription factor NF-ATc1 regulates lymphocyte proliferation and Th2 cytokine production. Immunity 1998;8:115–124.PubMedCrossRefGoogle Scholar
  47. 47.
    Hodge MR, Ranger AM, Charles de la Brousse F, Hoey T, Grusby MJ, Glimcher LH: Hyperproliferation and dysregulation of IL-4 expression in NF-ATp-deficient mice. Immunity 1996;4:397–405.PubMedCrossRefGoogle Scholar
  48. 48.
    Xanthoudakis S, Viola JP, Shaw KT, Luo C, Wallace JD, Bozza PT, et al.: An enhanced immune response in mice lacking the transcription factor NFAT1 [published erratum appears in Science 1996; 273(5280):1 325]. Science 1996; 272:892–895.PubMedCrossRefGoogle Scholar
  49. 49.
    Hodge MR, Chun HJ, Rengarajan J, Alt A, Lieberson R, Glimcher LH. NF-AT-driven interleukin-4 transcription potentiated by NIP45. Science 1996;274:1903–1905.PubMedCrossRefGoogle Scholar
  50. 50.
    Dong C, Yang DD, Wysk M, Whitmarsh AJ, Davis RJ, Flavell RA: Defective T cell differentiation in the absence of Jnkl. Science 1998; 282:2092–2095.PubMedCrossRefGoogle Scholar
  51. 51.
    Chow CW, Rincon M, Cayanagh J, Dickens M, Davis RJ: Nuclear accumulation of NFAT4 opposed by the JNK signal transduction pathway. Science 1997;278: 1638–1641.PubMedCrossRefGoogle Scholar
  52. 52.
    Li B, Tournier C, Davis RJ, Flavell RA: Regulation of IL-4 expression by the transcription factor JunB during T helper cell differentiation. EMBO J 1999;18:420–432.PubMedCrossRefGoogle Scholar
  53. 53.
    Rincon M, Derijard B, Chow CW, Davis RJ, Flavell RA: Reprogramming the signalling requirement for AP-1 (activator protein-1) activation during differentiation of precursor CD4+T-cells into effector Th1 and Th2 cells. Genes Function 1997;1:51–68.Google Scholar
  54. 54.
    Ho IC, Hodge MR, Rooney JW, Glimcher LH: The proto-oncogene c-maf is responsible for tissue-specific expression of interleukin-4. Cell 1996;85(7):973–983.PubMedCrossRefGoogle Scholar
  55. 55.
    Ho IC, Lo D, Glimcher LH: c-maf promotes T helper cell type 2 (Th2) and attenuates Th1 differentiation by both interleukin 4-dependent and-independent mechanisms. J Exp Med 1998; 188(10):1859–1866.PubMedCrossRefGoogle Scholar
  56. 56.
    Kim JI, Ho IC, Grusby MJ, Glimcher LH: The transcription factor c-Maf controls the production of interleukin-4 but not other Th2 cytokines. Immunity 1999;10(6): 745–751.PubMedCrossRefGoogle Scholar
  57. 57.
    Hsieh CS, Macatonia SE, Tripp CS, Wolf SF, O'Garra A, Murphy KM: Development of TH1 CD4+T cells through IL-12 produced by Listeria-induced macrophages. Science 1993;260(5107):547–549.PubMedCrossRefGoogle Scholar
  58. 58.
    Magram J, Connaughton SE, Warrier RR, Carvajal DM, Wu CY, Ferrante J, et al.: IL-12-deficient mice are defective in IFN gamma production and type 1 cytokine responses. Immunity 1996;4(5): 471–481.PubMedCrossRefGoogle Scholar
  59. 59.
    Piccotti JR, Li K, Chan SY, Ferrante J, Magram J, Eichwald EJ, et al.: Alloantigen-reactive Th1 development in IL-12-deficient mice. J Immunol 1998;160:1132–1138.PubMedGoogle Scholar
  60. 60.
    de Jong R, Altare F, Haagen IA, Elferink DG, van Boer T, Vriesman PJ, et al.: Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients. Science 1998;280:1435–1438.PubMedCrossRefGoogle Scholar
  61. 61.
    Altare F, Durandy A, Lammas D, Emile JF, Lamhamedi S, Le Deist F, et al.: Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency. Science 1998;280:1432–1435.PubMedCrossRefGoogle Scholar
  62. 62.
    Trinchieri G, Scott P: Interleukin-12: a proinflammatory cytokine with immunoregulatory functions. Res Immunol 1995;146(7–8): 423–431.PubMedCrossRefGoogle Scholar
  63. 63.
    Chua AO, Chizzonite R, Desai BB, Truitt TP, Nunes P, Minetti LJ, et al.: Expression cloning of a human IL-12 recepter component. A new member of the cytokine receptor superfamily with strong homology togpl30. J Immunol 1994;153(1):128–136.PubMedGoogle Scholar
  64. 64.
    Presky DH, Yang H, Minetti LJ, Chua AO, Nabavi N, Wu CY, et al.: A functional interleukin 12 receptor complex is composed of two beta-type cytokine receptor subunits. Proc Natl Acad Sci USA 1996;93(24):14,002–14,007.CrossRefGoogle Scholar
  65. 65.
    Szabo SJ, Dighe AS, Gubler U, Murphy KM: Regulation of the interleukin (IL)-12R beta 2 subunit expression in developing T helper1 (Th1) and Th2 cells. J Exp Med 1997;185(5):817–824.PubMedCrossRefGoogle Scholar
  66. 66.
    Naeger LK, McKinney J, Salvekar A, Hoey T: Identification of a STAT4 binding site in the interleukin-12 receptor required for signaling. J Biol Chem 1999; 274(4):1875–1878.PubMedCrossRefGoogle Scholar
  67. 67.
    Jacobson NG, Szabo SJ, Weher-Nordt RM, Zhong Z, Schreiber RD, Darnell JE Jr et al.: Interleukin 12 signaling in T helper type 1 (Th1) cells involves tyrosine phosphorylation of signal transducer and activator of transcription (Stat)3 and Stat4. J Exp Med 1996; 181(5):1755–1762.CrossRefGoogle Scholar
  68. 68.
    Kaplan MH, Sun YL, Hoey T, Grusby MJ: Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice. Nature 1999;382(6587): 174–177.CrossRefGoogle Scholar
  69. 69.
    Oyang W, Jacobson NG, Bhattacharya D, Gorham JD, Fenoglio D, Sha WC, et al.: The Ets transcription factor ERM is Th1-specific and induced by IL-12 through a Stat4-dependent pathway. Proc Natl Acad Sci USA 1999;96(7):3888–3893.CrossRefGoogle Scholar
  70. 70.
    Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH: A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 2000;100(6):655–669.PubMedCrossRefGoogle Scholar
  71. 71.
    Szabo SJ, Sullivan BM, Stemmann C, Satoskar AR, Sleckman BP, Glimcher LH: Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells. Science 2002;295(5553):338–342.PubMedCrossRefGoogle Scholar
  72. 72.
    Mullen AC, High FA, Hutchins AS, Lee HW, Villarino AV, Livingston DM, et al.: Role of T-bet in commitment of TH1 cells before IL-12-dependent selection. Science 2001; 292(5523):1907–1910.PubMedCrossRefGoogle Scholar
  73. 73.
    Rodriguez-Palmero M, Hara T, Thumbs A, Hunig T: Triggering of T cell proliferation through CD28 induces GATA-3 and promotes T helper type 2 differentiation in vitro and in vivo. Eur J Immunol 1999;29(12):3914–3924.PubMedCrossRefGoogle Scholar
  74. 74.
    Chen CH, Zhang DH, LaPorte JM, Ray A: Cyclic AMP activates p38 mitogen-activated protein kinase in Th2 cells: phosphorylation of GATA-3 and stimulation of Th2 cytokine gene expression. J Immunol 2000;165(10): 5597–5605.PubMedGoogle Scholar
  75. 75.
    Gorelik L, Fields PE, Flavell RA: Cutting edge: TGF-beta inhibits Th type 2 development through inhibition of GATA-3 expression. J Immunol 2000;165(9):4773–4777.PubMedGoogle Scholar
  76. 76.
    Heath VL, Murphy EE, Crain C, Tomlinson MG, O'Garra A: TGF-betal down-regulates Th2 development and results in decreased IL-4-induced STAT6 activation and GATA-3 expression. Eur J Immunol 2000;30(9):2639–2649.PubMedCrossRefGoogle Scholar
  77. 77.
    Blokzijl A, ten Dijke P, Ibanez CF: Physical and functional interaction between GATA-3 and Smad3 allows TGF-beta regulation of GATA target genes. Curr Biol 2002;12(1):35–45.PubMedCrossRefGoogle Scholar
  78. 78.
    Lee HJ, Takemoto N, Kurata H, Kamogawa Y, Miyatake S, O'Garra A, et al.: GATA-3 induces T helper cell type 2 (Th2) cytokine expression and chromatin remodeling in committed Th1 cells. J Exp Med 2000;192(1):105–115.PubMedCrossRefGoogle Scholar
  79. 79.
    Zhou M, Ouyang W, Gong Q, Katz SG, White JM, Orkin SH, et al.: Friend of GATA-1 represses GATA-3-dependent activity in CD4+ T cells. J Exp Med 2001; 194(10):1461–1471.PubMedCrossRefGoogle Scholar
  80. 80.
    Ranganath S, Murphy KM: Structure and specificity of GATA proteins in Th2 development. Mol Cell Biol 2001;21(8):2716–2725.PubMedCrossRefGoogle Scholar
  81. 81.
    Dasen JS, O'Connell SM, Flynn SE, Treier M, Gleiberman AS, Szeto DP, et al.: Reciprocal interactions of Pitl and GATA2 mediate signaling gradient-induced determination of pituitary cell types. Cell 1999;97:587–598.PubMedCrossRefGoogle Scholar
  82. 82.
    Tsai SF, Strauss E, Orkin SH: Functional analysis and in vivo foot printing implicate the erythroid transcription factor GATA-1 as a positive regulator of its own promoter. Genes Dev 1991;5(6): 919–931.PubMedGoogle Scholar
  83. 83.
    Das J, Chen CH, Yang L, Cohn L, Ray P, Ray A: A critical role for NF-kappa B in GATA 3 expression and TH2 differentiation in allergic airway inflammation. Nat Immunol 2001;2(1):45–50.PubMedCrossRefGoogle Scholar
  84. 84.
    Tsang AP, Visvader JE, Tumer CA, Fujiwara Y, Yu C, Weiss MJ, et al.: FOG, a multitype zinc finger protein, acts as a cofactor for transcription factor GATA-1 inerythroid and megakaryocytic differentiation. Cell 1997;90(1):109–119.PubMedCrossRefGoogle Scholar
  85. 85.
    Tsang AP, Fujiwara Y, Hom DB, Orkin SH: Failure of megakary-opoiesis and arrested erythropoiesis in mice lacking the GATA-1 transcriptional cofactor FOG. Genes Dev 1998;12(8):1176–1188.PubMedGoogle Scholar
  86. 86.
    Cubadda Y, Heitzler P, Ray RP, Bourouis M, Ramain P, Gelbart W, et al.: U-Shaped encodes a zinc finger protein that regulates the proneural genes achaete and scute during the formation of bristles in Drosophila. Genes Dev 1997; 11(22):3083–3095.PubMedGoogle Scholar
  87. 87.
    Tevosian SG, Deconinck AE, Cantor AB, Rieff HI, Fujiwara Y, Corfas G, et al.: FOG-2: a novel GATA-family cofactor related to multitype zinc-finger proteins friend of GATA-1 and U-shaped. Proc Natl Acad Sci USA 1999; 96(3):950–955.PubMedCrossRefGoogle Scholar
  88. 88.
    Svensson EC, Tufts RL, Polk CE, Leiden JM: Molecular cloning of FOG-2: a modulator of transcription factor GATA-4 in cardiomyocytes. Proc Natl Acad Sci USA 1999;96(3):956–961.PubMedCrossRefGoogle Scholar
  89. 89.
    Miaw SC, Choi A, Yu E, Kishikawa H, Ho IC: ROG, repressor of GATA, regulates the expression of cytokine genes. Immunity 2000; 12(3):323–333.PubMedCrossRefGoogle Scholar
  90. 90.
    Dent AL, Shaffer AL, Yu X, Allman D, Staudt LM: Control of inflammation, cytokine expression, and germinal center formation by BCL. Science 1997;276(5312):589–592.PubMedCrossRefGoogle Scholar
  91. 91.
    Dent AL, Hu-Li J, Paul WE, Staudt LM: T helper type 2 inflammatory disease in the absence of interleukin 4 and transcription factor STAT6. Proc Natl Acad Sci USA 1998;95(23):13,823–13,828.CrossRefGoogle Scholar
  92. 92.
    Toney LM, Cattoretti G, Graf JA, Merghoub T, Pandolfi PP, Dalla-Favera R, et al.: BCL-6 regulates chemokine kene transcription in macrophages. Nat Immunol 2000; 1(3):214–220.PubMedCrossRefGoogle Scholar
  93. 93.
    Gourley T, Roys S, Lukacs NW, Kunkel SL, Flavell RA, Chang CH: A novel role for the major histocompatibility complex class II transactivator CIITA in the repression of IL-4 production. Immunity 1999;10(3):377–386.PubMedCrossRefGoogle Scholar
  94. 94.
    Nakamura Y, Ghaffar O, Olivenstein R, Taha RA, Soussi-Gounni A, Zhang DH, et al.: Gene expression of the GATA-3 transcription factor is increased in atopic asthma. J Allergy Clin Immunol 1999; 103(2):215–222.PubMedCrossRefGoogle Scholar
  95. 95.
    Finotto S, De Sanctis GT, Lehr HA, Herz U, Buerke M, Schipp M, et al. Treatment of allergic airway inflammation and hyperresponsiveness by antisense-induced local blockade of GATA-3 expression. J Exp Med 2001;193(11): 1247–1260.PubMedCrossRefGoogle Scholar
  96. 96.
    Zhang DH, Yang L, Cohn L, Parkyn L, Homer R, Ray P, et al.: Inhibition of allergic inflammation in a murine model of asthma by expression of adominant-negative mutant of GATA-3. Immunity 1999;11(4): 473–482.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2003

Authors and Affiliations

  • Meixia Zhou
    • 1
  • Wenjun Ouyang
    • 2
  1. 1.Department of PathologyWashington University School of MedicineSt. Louis
  2. 2.Department of ImmunologyGenentech, Inc.South San Francisco

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