Conditional deletion of Gata3 shows its essential function in T(H)1-T(H)2 responses.
Expression of the transcription factor GATA-3 is strongly associated with T helper type 2 (T(H)2) 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 T(H)2 cell differentiation; without GATA-3, T(H)1 differentiation occurred in the absence of IL-12 and interferon-gamma. Gata3 deletion limited the growth of T(H)2 cells but not T(H)1 cells. Deletion of Gata3 from established T(H)2 cells abolished IL-5 and IL-13 but not IL-4 production. In vivo deletion of Gata3 using OX40-Cre eliminated T(H)2 responses and allowed the development of interferon-gamma-producing cells in mice infected with Nippostrongylus brasiliensis. Thus, GATA-3 serves as a principal switch in determining T(H)1-T(H)2 responses.
Zhu
Jinfang
J
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. jfzhu@niaid.nih.gov <jfzhu@niaid.nih.gov>
Min
Booki
B
Hu-Li
Jane
J
Watson
Cynthia J
CJ
Grinberg
Alex
A
Wang
Qi
Q
Killeen
Nigel
N
Urban
Joseph F
JF
Guo
Liying
L
Paul
William E
WE
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology / Q000502:physiology; D002455:Cell Division / Q000276:immunology / Q000502:physiology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D050990:GATA3 Transcription Factor; D017353:Gene Deletion; D051379:Mice; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics* / Q000276:immunology
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D015534:Trans-Activators