The Transcription Factor GATA3 Is Critical for the Development of All IL-7Rα-Expressing Innate Lymphoid Cells

被引:322
作者
Yagi, Ryoji [1 ]
Zhong, Chao [1 ]
Northrup, Daniel L. [2 ]
Yu, Fang [1 ]
Bouladoux, Nicolas [3 ]
Spencer, Sean [3 ]
Hu, Gangqing [2 ]
Barron, Luke [3 ]
Sharma, Suveena [1 ]
Nakayama, Toshinori [4 ]
Belkaid, Yasmine [3 ]
Zhao, Keji [2 ]
Zhu, Jinfang [1 ]
机构
[1] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA
[2] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA
[3] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA
[4] Chiba Univ, Grad Sch Med, Dept Immunol, Chiba 2608670, Japan
关键词
ROR-GAMMA-T; EXPRESSION; FETAL; BET; GENERATION; POPULATION; CYTOKINES; ELICITS; DRIVES; ALPHA;
D O I
10.1016/j.immuni.2014.01.012
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Innate lymphoid cells (ILCs) are critical in innate immune responses to pathogens and lymphoid organ development. Similar to CD4(+) T helper (Th) cell subsets, ILC subsets positive for interleukin-7 receptor alpha (IL-7R alpha) produce distinct sets of effector cytokines. However, the molecular control of IL-7R alpha(+) ILC development and maintenance is unclear. Here, we report that GATA3 was indispensable for the development of all IL-7R alpha(+) ILC subsets and T cells but was not required for the development of classical natural killer cells. Conditionally Gata3-deficient mice had no lymph nodes and were susceptible to Citrobactor rodentium infection. After the ILCs had fully developed, GATA3 remained important for the maintenance and functions of ILC2s. Genome-wide gene expression analyses indicated that GATA3 regulated a similar set of cytokines and receptors in Th2 cells and ILC2s, but not in ILC3s. Thus, GATA3 plays parallel roles in regulating the development and functions of CD4(+) T cells and IL-7R alpha(+) ILCs.
引用
收藏
页码:378 / 388
页数:11
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