Zhu Jinfang, Min Booki, Hu-Li Jane, Watson Cynthia J, Grinberg Alex, Wang Qi, Killeen Nigel, Urban Joseph F, Guo Liying, Paul William E
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nat Immunol. 2004 Nov;5(11):1157-65. doi: 10.1038/ni1128. Epub 2004 Oct 10.
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.
转录因子GATA-3的表达与2型辅助性T细胞（T(H)2）分化密切相关，但一直缺乏其参与这一过程的遗传学证据。在此，我们构建了一个条件性GATA-3缺陷小鼠品系。在体外敲除Gata3可减少白细胞介素4（IL-4）依赖型和IL-4非依赖型T(H)2细胞的分化；没有GATA-3时，在缺乏IL-12和干扰素-γ的情况下会发生T(H)1分化。敲除Gata3会限制T(H)2细胞的生长，但不会限制T(H)1细胞的生长。从已建立的T(H)2细胞中敲除Gata3可消除IL-5和IL-13的产生，但不会消除IL-4的产生。使用OX40-Cre在体内敲除Gata3可消除T(H)2反应，并使感染巴西日圆线虫的小鼠中产生干扰素-γ的细胞得以发育。因此，GATA-3是决定T(H)1-T(H)2反应的主要开关。
