Interleukin-33-activated basophils promote asthma by regulating Th2 cell entry into lung tissue

Area of Science:

• Immunology
• Allergy Research
• Respiratory Medicine

Background:

• Asthma involves lung eosinophilia, remodeling, and mucus plugging, regulated by Th2 cells.
• House dust mite (HDM) inhalation activates innate immune cells, promoting Th2 adaptive immunity.

Purpose of the Study:

• To investigate the role of basophils in the development of type 2 immunity and allergic airway inflammation in response to HDM.
• To elucidate the mechanisms by which basophils contribute to asthma pathogenesis.

Main Methods:

• Used C57Bl/6 mice exposed to HDM inhalation.
• Employed conditional basophil depletion during sensitization and allergen challenge phases.
• Analyzed basophil-intrinsic IL-33/ST2 signaling and Tnfaip3 function.
• Assessed Th2 cell recruitment and airway inflammation markers.

Main Results:

• Basophil depletion during allergen challenge, not sensitization, reduced asthma features.
• Basophil IL-4 production and Th2 cell lung recruitment were driven by IL-33/ST2 signaling, not FcεRI.
• Loss of Tnfaip3 in basophils exacerbated asthma symptoms.
• IL-33-activated basophils control Th2 cell entry into lung tissue.

Conclusions:

• Basophils act as critical gatekeepers, modulating Th2 cell entry into the lungs during allergic airway inflammation.
• IL-33-activated basophils play a pivotal role in boosting allergic asthma responses.
• Targeting basophil-IL-33 signaling may offer therapeutic strategies for asthma.