Cutting Edge: Core Binding Factor β Is Required for Group 2 Innate Lymphoid Cell Activation.

Area of Science:

• Immunology
• Molecular Biology
• Cell Biology

Background:

• Group 2 innate lymphoid cells (ILC2) are crucial innate immune cells involved in allergic responses and asthma.
• Mature ILC2 rapidly release type-2 cytokines upon activation, but the underlying molecular mechanisms remain unclear.

Purpose of the Study:

• To investigate the role of core binding factor β (CBFβ) in the activation of ILC2.
• To elucidate the molecular pathways by which CBFβ regulates ILC2 function.

Main Methods:

• Investigated CBFβ function in ILC2 homeostasis and allergic airway inflammation using genetic deletion and pharmacological inhibition in mouse models.
• Analyzed gene and protein expression of key ILC2 effector molecules.
• Performed chromatin immunoprecipitation to assess direct binding of the CBF transcriptional complex to target gene promoters and enhancers.
• Assessed ribosome biogenesis and protein translation in activated ILC2.

Main Results:

• CBFβ deficiency or inhibition did not affect ILC2 maintenance but abolished their activation during allergic airway inflammation.
• CBFβ inhibition ameliorated ILC2-mediated airway hyperresponsiveness in a mouse model of acute allergen inhalation.
• CBFβ was found to directly regulate the transcription of key ILC2 genes, including Il13 and Vegfa.
• CBFβ enhanced ribosome biogenesis and promoted gene translation in activated ILC2.

Conclusions:

• Core binding factor β (CBFβ) is indispensable for ILC2 activation, not their homeostasis.
• CBFβ controls ILC2 effector functions by regulating both gene transcription and protein translation.
• Targeting CBFβ represents a potential therapeutic strategy for allergic diseases driven by ILC2.