Journal article
IL-5 antagonism reverses priming and activation of eosinophils in severe eosinophilic asthma
- Abstract:
- Eosinophils are key effector cells mediating airway inflammation and exacerbation in patients with severe eosinophilic asthma. They are present in increased numbers and activation states in the airway mucosa and lumen. Interleukin-5 (IL-5) is the key eosinophil growth factor that is thought to play a role in eosinophil priming and activation. However, the mechanism of these effects is still not fully understood. The anti-IL-5 antibody mepolizumab reduces eosinophil counts in the airway modestly but has a large beneficial effect on the frequency of exacerbations of severe eosinophilic asthma, suggesting that reduction in eosinophil priming and activation is of central mechanistic importance. In this study, we used the therapeutic effect of mepolizumab and single-cell ribonucleic acid sequencing to investigate the mechanism of eosinophil priming and activation by IL-5. We demonstrated that IL-5 is a dominant driver of eosinophil priming and plays multifaceted roles in eosinophil function. It enhances eosinophil responses to other stimulators of migration, survival, and activation by activating phosphatidylinositol-3-kinases, extracellular signal-regulated kinases, and p38 mitogen-activated protein kinases signaling pathways. It also enhances the pro-fibrotic roles of eosinophils in airway remodeling via transforming growth factor-β pathway. These findings provide a mechanistic understanding of eosinophil priming in severe eosinophilic asthma and the therapeutic effect of anti-IL-5 approaches in the disease.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 2.1MB, Terms of use)
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- Publisher copy:
- 10.1016/j.mucimm.2024.03.005
Authors
+ National Institute for Health and Care Excellence
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- Funder identifier:
- https://ror.org/015ah0c92
- Grant:
- WT222426/Z/21/Z
- Publisher:
- Elsevier
- Journal:
- Mucosal Immunology More from this journal
- Volume:
- 17
- Issue:
- 4
- Pages:
- 524-536
- Place of publication:
- United States
- Publication date:
- 2024-03-15
- Acceptance date:
- 2024-03-11
- DOI:
- EISSN:
-
1935-3456
- ISSN:
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1933-0219
- Pmid:
-
38493955
- Language:
-
English
- Pubs id:
-
1836232
- Local pid:
-
pubs:1836232
- Deposit date:
-
2024-12-18
- ARK identifier:
Terms of use
- Copyright holder:
- Luo et al
- Copyright date:
- 2024
- Rights statement:
- © 2024 The Authors. Published by Elsevier Inc. on behalf of Society for Mucosal Immunology. User License: Creative Commons Attribution (CC BY 4.0)
- Licence:
- CC Attribution (CC BY)
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