Conditional deletion of Gata3 shows its essential function in TH1-TH2 responses

Expression of the transcription factor GATA-3 is strongly associated with T helper type 2 (TH2) differentiation, but genetic evidence for its involvement in this process has been lacking.

Here, we generated a conditional GATA-3-deficient mouse line. In vitro deletion of Gata3 diminished both interleukin 4 (IL-4)–dependent and IL-4-independent TH2 cell differentiation; without

GATA-3, TH1 differentiation occurred in the absence of IL-12 and interferon-γ. Gata3 deletion limited the growth of TH2 cells but not TH1 cells. Deletion of Gata3 from established TH2 cells

abolished IL-5 and IL-13 but not IL-4 production. In vivo deletion of Gata3 using OX40-Cre eliminated TH2 responses and allowed the development of interferon-γ-producing cells in mice

infected with Nippostrongylus brasiliensis. Thus, GATA-3 serves as a principal switch in determining TH1-TH2 responses.

We thank H. Gu (Columbia University, New York, New York) for providing pL2-Neo vector and advice on targeting vector construction; H. Westphal (National Institute of Child Health and Human

Development, Bethesda, Maryland) and C.B. Wilson (University of Washington, Seattle, Washington) for providing C57BL/6EIIa-Cre and CD4-Cre transgenic mice, respectively; D.R. Littman (New

York University School of Medicine, New York, New York), T. Kitamura (University of Tokyo, Tokyo, Japan), K.M. Murphy (Washington University, St. Louis, Missouri), W.C. Sha (University of

California, Berkeley, California) and G.P. Nolan (Stanford University School of Medicine, Stanford, California) for providing MSCV-Cre, pMX-STAT5A1*6, GFP-RV, MSCV-IRES-tNGFR (NGFR-RV) and

the Phoenix-Eco packaging cell line, respectively; T. Moyer (National Institute of Allergy and Infectious Diseases, Flow Cytometry Unit) for cell sorting; and S. Starnes for editorial

assistance.

Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, Maryland, USA

Jinfang Zhu, Booki Min, Jane Hu-Li, Cynthia J Watson, Liying Guo & William E Paul

Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, 94143, California, USA

US Department of Agriculture, Nutrient Requirements and Functions Laboratory, Beltsville Human Nutrition Research Center, Beltsville, 20705, Maryland, USA

Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, 20892, Maryland, USA

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