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

Asthma is characterized by lung eosinophilia, remodeling, and mucus plugging, controlled by adaptive Th2 effector cells secreting IL-4, IL-5, and IL-13. Inhaled house dust mite (HDM) causes the release of barrier epithelial cytokines that activate various innate immune cells like DCs and basophils that can promote Th2 adaptive immunity directly or indirectly. Here, we show that basophils play a crucial role in the development of type 2 immunity and eosinophilic inflammation, mucus production, and bronchial hyperreactivity in response to HDM inhalation in C57Bl/6 mice. Interestingly, conditional depletion of basophils during sensitization did not reduce Th2 priming or asthma inception, whereas depletion during allergen challenge did. During the challenge of sensitized mice, basophil-intrinsic IL-33/ST2 signaling, and not FcεRI engagement, promoted basophil IL-4 production and subsequent Th2 cell recruitment to the lungs via vascular integrin expression. Basophil-intrinsic loss of the ubiquitin modifying molecule Tnfaip3, involved in dampening IL-33 signaling, enhanced key asthma features. Thus, IL-33-activated basophils are gatekeepers that boost allergic airway inflammation by controlling Th2 tissue entry.

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Publication Details

Journal
The Journal of Experimental Medicine
Published
2024-09-19
DOI
https://doi.org/10.1084/jem.20240103
Citations
28
Primary Topic
IL-33, ST2, and ILC Pathways
Type
article
Field-Weighted Citation Impact
6.73

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article

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

Fabian Bick, Hamida Hammad, Geert Loo, Justine Van Moorleghem et al.
28 citations
The Journal of Experimental Medicine
IL-33, ST2, and ILC Pathways
6.73
article

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

Fabian Bick, Hamida Hammad, Geert Loo, Justine Van Moorleghem, David Voehringer, Manon Vanheerswynghels, Richard M. Locksley, Bart N. Lambrecht, Rudi Beyaert, Martijn J. Schuijs, C. Gómez
article en
28 citations

Abstract

Asthma is characterized by lung eosinophilia, remodeling, and mucus plugging, controlled by adaptive Th2 effector cells secreting IL-4, IL-5, and IL-13. Inhaled house dust mite (HDM) causes the release of barrier epithelial cytokines that activate various innate immune cells like DCs and basophils that can promote Th2 adaptive immunity directly or indirectly. Here, we show that basophils play a crucial role in the development of type 2 immunity and eosinophilic inflammation, mucus production, and bronchial hyperreactivity in response to HDM inhalation in C57Bl/6 mice. Interestingly, conditional depletion of basophils during sensitization did not reduce Th2 priming or asthma inception, whereas depletion during allergen challenge did. During the challenge of sensitized mice, basophil-intrinsic IL-33/ST2 signaling, and not FcεRI engagement, promoted basophil IL-4 production and subsequent Th2 cell recruitment to the lungs via vascular integrin expression. Basophil-intrinsic loss of the ubiquitin modifying molecule Tnfaip3, involved in dampening IL-33 signaling, enhanced key asthma features. Thus, IL-33-activated basophils are gatekeepers that boost allergic airway inflammation by controlling Th2 tissue entry.

The Journal of Experimental MedicineVol. 221(12)
University of California, San Francisco (US), Ghent University Hospital (BE), Erasmus MC (NL), Ghent University (BE), Universitätsklinikum Erlangen (DE), VIB-UGent Center for Inflammation Research (BE), Erasmus University Rotterdam (NL)
King Baudouin Foundation United States, Fondation Acteria, European Commission, Fonds Wetenschappelijk Onderzoek, Universiteit Gent, Vlaams Instituut voor Biotechnologie, Koning Boudewijnstichting, European Research Council, H2020 Marie Skłodowska-Curie Actions
Openalex Percentile: Top 2%
IL-33, ST2, and ILC Pathways
6.73
DOIOpen Access PDFOpenAlex
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