Critical role of p38 and GATA3 in natural helper cell function.
Critical role of p38 and GATA3 in natural helper cell function.
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DOI：
10.4049/jimmunol.1300379
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发表时间：
2013-08-15
期刊：
影响因子：
--
通讯作者：
Koyasu S
中科院分区：
文献类型：
--
作者：
Furusawa J;Moro K;Motomura Y;Okamoto K;Zhu J;Takayanagi H;Kubo M;Koyasu S
自然辅助细胞（NH）是Lin−IL-2 R +IL-7 R +IL-25 R +IL-33 R + GATA 3+第2组先天性淋巴样细胞亚群的成员，其特征是表达转录因子GATA 3和RORα，并在IL-33刺激或IL-2和IL-25联合刺激时产生大量Th 2细胞因子，如IL-5、IL-6和IL-13。本文研究了NH细胞中细胞因子表达和发育的信号转导途径。用IL-33或IL-2和IL-25的组合刺激诱导NH细胞中的p38活化和GATA 3的磷酸化，并且GATA 3的磷酸化形式结合到IL-5和IL-13启动子。所有这些事件都被p38抑制剂SB 203580阻断。抑制p38也会阻止IL-6的产生。缺乏Gata 3的成熟NH细胞在IL-5和IL-13的增殖和产生方面受损，但在IL-6方面不受损，这表明p38和GATA 3对于IL-5和IL-13的增殖和产生都是关键的，并且p38下游的机制在IL-6和IL-5/IL-13之间不同。与此相反，缺乏RORα的NH细胞的增殖和细胞因子的产生没有受到影响，表明GATA 3而不是RORα在成熟NH细胞的效应器功能中起关键作用。然而，造血干细胞中GATA 3或RORα的缺失分别阻断了向NH细胞的发育。我们的研究结果表明p38和GATA 3在NH细胞功能中的重要作用。
Natural helper (NH) cells, a member of Lin−IL-2R+IL-7R+IL-25R+IL-33R+GATA3+ group 2 innate lymphoid cell subset, are characterized by the expression of transcription factors GATA3 and RORα and production of large amounts of Th2 cytokines such as IL-5, IL-6 and IL-13 upon IL-33 stimulation or a combination of IL-2 and IL-25. We studied in this paper the signal transduction pathway(s) critical for the cytokine expression and development of NH cell. Either stimulation with IL-33 or a combination of IL-2 and IL-25 induced p38 activation and phosphorylation of GATA3 in NH cells, and the phosphorylated form of GATA3 bound to the IL-5 and IL-13 promoters. All of these events were blocked by SB203580, a p38 inhibitor. Inhibition of p38 also blocked IL-6 production. The mature NH cells lacking Gata3 were impaired in the proliferation and production of IL-5 and IL-13 but not IL-6, indicating that both p38 and GATA3 are critical for the proliferation and production of IL-5 and IL-13 and that the mechanisms downstream of p38 differ between IL-6 and IL-5/IL-13. In contrast, the NH cells lacking RORα showed no impairment in the proliferation and cytokine production, indicating that GATA3 but not RORα plays a pivotal role in the effector functions of mature NH cell. However, deletion of either GATA3 or RORα in hematopoietic stem cells severally blocked the development into NH cells. Our results demonstrate the important roles of p38 and GATA3 in NH cell functions.
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DOI：
10.1084/jem.20092176
发表时间：
2009-12-21
期刊：
The Journal of experimental medicine
影响因子：
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作者：
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