Department of Immunology and Microbial Diseases, Albany Medical College, Albany, NY 12208.
Division of Allergy, Asthma and Immunology, Department of Medicine, Albany Medical Center, Albany, NY 12203.
J Immunol. 2019 Mar 15;202(6):1669-1673. doi: 10.4049/jimmunol.1800852. Epub 2019 Feb 6.
Group 2 innate lymphoid cells (ILC2) are tissue-resident, long-lived innate effector cells implicated in allergy and asthma. Upon activation, mature ILC2 rapidly secrete large amounts of type-2 cytokines and other effector molecules. The molecular pathways that drive ILC2 activation are not well understood. In this study, we report that the transcriptional controller core binding factor β (CBFβ) is required for ILC2 activation. Deletion or inhibition of CBFβ did not impair the maintenance of ILC2 at homeostasis but abolished ILC2 activation during allergic airway inflammation. Treatment with CBFβ inhibitors prevented ILC2-mediated airway hyperresponsiveness in a mouse model of acute allergen inhalation. CBFβ promoted expression of key ILC2 genes at both transcriptional and translational levels. CBF transcriptional complex directly bound to and promoters and enhancers, and controlled gene transcription. CBFβ further promoted ribosome biogenesis and enhanced gene translation in activated ILC2. Together, these data establish an essential role for CBFβ in ILC2 activation.
2 型固有淋巴细胞（ILC2）是组织驻留的、寿命长的固有效应细胞，参与过敏和哮喘的发生。成熟的 ILC2 被激活后会迅速大量分泌 2 型细胞因子和其他效应分子。驱动 ILC2 激活的分子途径尚不清楚。在这项研究中，我们报告转录控制器核心结合因子 β（CBFβ）对于 ILC2 的激活是必需的。CBFβ 的缺失或抑制并不损害 ILC2 在体内平衡时的维持，但在过敏性气道炎症期间消除了 ILC2 的激活。在急性过敏原吸入的小鼠模型中，使用 CBFβ 抑制剂可预防 ILC2 介导的气道高反应性。CBFβ 在转录和翻译水平上促进关键的 ILC2 基因的表达。CBF 转录复合物直接与 和 启动子和增强子结合，控制基因转录。CBFβ 进一步促进激活的 ILC2 中的核糖体生物发生并增强基因翻译。总之，这些数据确立了 CBFβ 在 ILC2 激活中的重要作用。
