Interleukin-33-activated basophils promote asthma by regulating Th2 cell entry into lung tissue
- Author
- Martijn Schuijs (UGent) , Claudia Mariela Brenis Gómez (UGent) , Fabian Bick (UGent) , Justine Van Moorleghem (UGent) , Manon Vanheerswynghels (UGent) , Geert van Loo (UGent) , Rudi Beyaert (UGent) , David Voehringer, Richard M. Locksley, Hamida Hammad (UGent) and Bart Lambrecht (UGent)
- Organization
- Project
-
- The role of alternatively-activated macrophages in the development of a lung pre-metastatic niche
- Taking IBD Genes from GWAS to Function to Drug Target
- An integrated approach to unravel eosinophil function in chronic eosinophilic disorders
- Role of damage associated molecular patterns (DAMPs) in initiation and persistence of chronic airway inflammation
- Understanding the immunological basis of persistent airway obstruction in asthma
- 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 Fc epsilon RI 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.
- Keywords
- HOUSE-DUST MITE, CLASS-II COMPLEXES, DENDRITIC CELLS, TYPE-2 IMMUNITY, MAST-CELLS, IL-4 PRODUCTION, IN-VITRO, RESPONSES, CYTOKINE, INDUCTION
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01J96GNV2WT7DCAW2RR1CACHRQ
- MLA
- Schuijs, Martijn, et al. “Interleukin-33-Activated Basophils Promote Asthma by Regulating Th2 Cell Entry into Lung Tissue.” JOURNAL OF EXPERIMENTAL MEDICINE, vol. 221, no. 12, 2024, doi:10.1084/jem.20240103.
- APA
- Schuijs, M., Brenis Gómez, C. M., Bick, F., Van Moorleghem, J., Vanheerswynghels, M., van Loo, G., … Lambrecht, B. (2024). Interleukin-33-activated basophils promote asthma by regulating Th2 cell entry into lung tissue. JOURNAL OF EXPERIMENTAL MEDICINE, 221(12). https://doi.org/10.1084/jem.20240103
- Chicago author-date
- Schuijs, Martijn, Claudia Mariela Brenis Gómez, Fabian Bick, Justine Van Moorleghem, Manon Vanheerswynghels, Geert van Loo, Rudi Beyaert, et al. 2024. “Interleukin-33-Activated Basophils Promote Asthma by Regulating Th2 Cell Entry into Lung Tissue.” JOURNAL OF EXPERIMENTAL MEDICINE 221 (12). https://doi.org/10.1084/jem.20240103.
- Chicago author-date (all authors)
- Schuijs, Martijn, Claudia Mariela Brenis Gómez, Fabian Bick, Justine Van Moorleghem, Manon Vanheerswynghels, Geert van Loo, Rudi Beyaert, David Voehringer, Richard M. Locksley, Hamida Hammad, and Bart Lambrecht. 2024. “Interleukin-33-Activated Basophils Promote Asthma by Regulating Th2 Cell Entry into Lung Tissue.” JOURNAL OF EXPERIMENTAL MEDICINE 221 (12). doi:10.1084/jem.20240103.
- Vancouver
- 1.Schuijs M, Brenis Gómez CM, Bick F, Van Moorleghem J, Vanheerswynghels M, van Loo G, et al. Interleukin-33-activated basophils promote asthma by regulating Th2 cell entry into lung tissue. JOURNAL OF EXPERIMENTAL MEDICINE. 2024;221(12).
- IEEE
- [1]M. Schuijs et al., “Interleukin-33-activated basophils promote asthma by regulating Th2 cell entry into lung tissue,” JOURNAL OF EXPERIMENTAL MEDICINE, vol. 221, no. 12, 2024.
@article{01J96GNV2WT7DCAW2RR1CACHRQ,
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 Fc epsilon RI 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.}},
articleno = {{e20240103}},
author = {{Schuijs, Martijn and Brenis Gómez, Claudia Mariela and Bick, Fabian and Van Moorleghem, Justine and Vanheerswynghels, Manon and van Loo, Geert and Beyaert, Rudi and Voehringer, David and Locksley, Richard M. and Hammad, Hamida and Lambrecht, Bart}},
issn = {{0022-1007}},
journal = {{JOURNAL OF EXPERIMENTAL MEDICINE}},
keywords = {{HOUSE-DUST MITE,CLASS-II COMPLEXES,DENDRITIC CELLS,TYPE-2 IMMUNITY,MAST-CELLS,IL-4 PRODUCTION,IN-VITRO,RESPONSES,CYTOKINE,INDUCTION}},
language = {{eng}},
number = {{12}},
pages = {{21}},
title = {{Interleukin-33-activated basophils promote asthma by regulating Th2 cell entry into lung tissue}},
url = {{http://doi.org/10.1084/jem.20240103}},
volume = {{221}},
year = {{2024}},
}
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