Core Binding Factor Is Required For Group-2 Innate Lymphoid Cell Activation

Group-2 innate lymphoid cells (ILC2) are tissue-resident, long-lived innate effector cells implicated in allergy and asthma. Upon activation, mature ILC2 rapidly secret large amounts of type-2 cytokines and other effector molecules. The molecular pathways that drive ILC2 activation are not well understood. Here we report that the transcriptional controller Core-binding factor (CBF) is required for ILC2 activation. Deletion or inhibition of CBF did not impair the maintenance of ILC2 at homeostasis, but abolished ILC2 activation during allergic airway inflammation. Treatment with CBF inhibitors prevented ILC2-mediated airway hyperresponsiveness in a mouse model of acute Alternaria allergen inhalation. CBF promoted expression of key ILC2 genes at both transcriptional and translational levels. CBF transcriptional complex directly bound to Il13 and Vegfa promoters and enhancers, and controlled gene transcription. CBF further promoted ribosome biogenesis and enhanced gene translation in activated ILC2. Together, these data establish an essential role for CBF in ILC2 activation.

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