Alternative activation generates IL-10 producing type 2 innate lymphoid cells.

Alternative activation generates IL-10 producing type 2 innate lymphoid cells.
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DOI:
10.1038/s41467-017-02023-z
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发表时间:
2017-12-01
影响因子:
16.6
通讯作者:
Kaye J
Kaye J
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Seehus CR;Kadavallore A;Torre B;Yeckes AR;Wang Y;Tang J;Kaye J

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2 型先天淋巴细胞 (ILC2) 与 CD4+ Th2 细胞共享细胞因子和转录因子表达,但 ILC2 谱系的功能多样性尚未得到充分探索。在这里,我们展示了活化肺 ILC2 分子上不同的子集的诱导,称为 ILC210。这些细胞产生 IL-10 并下调一些促炎基因。产生 ILC210 的信号与诱导 IL-13 产生的信号不同,基因表达数据表明另一种激活途径导致 ILC210 的产生。在体内,IL-2 增强 ILC210 的生成,并与肺部嗜酸性粒细胞募集减少相关。与大多数激活的 ILC2 不同,ILC210 群体在体内刺激停止后收缩,并维持可通过再刺激重新调用的子集,类似于 T 细胞效应细胞和记忆细胞的生成。这些数据证明了以前未被重视的产生IL-10的ILC2效应细胞群的产生。 2 型先天淋巴细胞 (ILC2) 被认为是产生 IL-5 和 IL-13 的统一效应细胞群。在这里,作者表明,在小鼠中,IL-33 可以选择性地激活这些细胞,产生分子上不同的产生 IL-10 的子集,命名为 ILC210。
Type 2 innate lymphoid cells (ILC2) share cytokine and transcription factor expression with CD4+ Th2 cells, but functional diversity of the ILC2 lineage has yet to be fully explored. Here, we show induction of a molecularly distinct subset of activated lung ILC2, termed ILC210. These cells produce IL-10 and downregulate some pro-inflammatory genes. Signals that generate ILC210 are distinct from those that induce IL-13 production, and gene expression data indicate that an alternative activation pathway leads to the generation of ILC210. In vivo, IL-2 enhances ILC210 generation and is associated with decreased eosinophil recruitment to the lung. Unlike most activated ILC2, the ILC210 population contracts after cessation of stimulation in vivo, with maintenance of a subset that can be recalled by restimulation, analogous to T-cell effector cell and memory cell generation. These data demonstrate the generation of a previously unappreciated IL-10 producing ILC2 effector cell population. Type 2 innate lymphoid cells (ILC2) are thought to be a uniform population of effector cells that produce IL-5 and IL-13. Here, the authors shown that, in mice, IL-33 can alternatively activate these cells to generate a molecularly distinct IL-10-producing subset designated ILC210.
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