IL-1 is a critical regulator of group 2 innate lymphoid cell function and plasticity
IL-1 is a critical regulator of group 2 innate lymphoid cell function and plasticity
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DOI：
10.1038/ni.3447
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发表时间：
2016-06-01
影响因子：
30.5
通讯作者：
Liu, Yong-Jun
中科院分区：
文献类型：
--
作者：
Ohne, Yoichiro;Silver, Jonathan S.;Liu, Yong-Jun
第2组先天性淋巴样细胞（ILC 2细胞）对于2型免疫应答是重要的，并且被上皮细胞因子白细胞介素33（IL-33）、IL-25和胸腺基质淋巴细胞生成素（TSLP）激活。在这里，我们证明了IL-1 β是ILC 2细胞的关键激活剂，诱导增殖和细胞因子产生，并调节上皮细胞因子受体的表达。IL-1 β还通过诱导转录因子T-bet和细胞因子受体链IL-12 R β 2的低表达来控制ILC 2可塑性，这使得这些细胞能够响应IL-12而转化为ILC 1表型。这种转变的标志是一个非典型的染色质景观，其特征是同时转录的基因座编码干扰素-γ（IFN-γ）和基因座编码IL-5和IL-13的可及性。最后，IL-1 β在体内增强ILC 2的活化和可塑性，IL-12充当决定ILC 2与ILC 1反应的开关。因此，我们已经确定了IL-1 β在促进ILC 2成熟和可塑性方面的一个先前未知的作用。
Group 2 innate lymphoid cells (ILC2 cells) are important for type 2 immune responses and are activated by the epithelial cytokines interleukin 33 (IL-33), IL-25 and thymic stromal lymphopoietin (TSLP). Here we demonstrated that IL-1 beta was a critical activator of ILC2 cells, inducing proliferation and cytokine production and regulating the expression of epithelial cytokine receptors. IL-1 beta also governed ILC2 plasticity by inducing low expression of the transcription factor T-bet and the cytokine receptor chain IL-12R beta 2, which enabled the conversion of these cells into an ILC1 phenotype in response to IL-12. This transition was marked by an atypical chromatin landscape characterized by the simultaneous transcriptional accessibility of the locus encoding interferon-gamma (IFN-gamma) and the loci encoding IL-5 and IL-13. Finally, IL-1 beta potentiated ILC2 activation and plasticity in vivo, and IL-12 acted as the switch that determined an ILC2-versus-ILC1 response. Thus, we have identified a previously unknown role for IL-1 beta in facilitating ILC2 maturation and plasticity.