期刊
ALLERGY
卷 77, 期 3, 页码 856-869出版社
WILEY
DOI: 10.1111/all.15072
关键词
asthma; asthma treatment; inflammation; interleukin
资金
- Deutsche Zentrum fur Lungenforschung
- Deutsche Forschungsgemeinschaft
- National Institutes of Health
- Bundesministerium fur Bildung und Forschung
The study found that IL-37 downregulates allergic airway inflammation by counterbalancing the disease-amplifying effects of IL-1 beta and IL-33.
Background Children with asthma have impaired production of interleukin (IL) 37; in mice, IL-37 reduces hallmarks of experimental allergic asthma (EAA). However, it remains unclear how IL-37 exerts its inhibitory properties in asthma. This study aimed to identify the mechanism(s) by which IL-37 controls allergic inflammation. Methods IL-37 target cells were identified by single-cell RNA-seq of IL-1R5 and IL-1R8. Airway tissues were isolated by laser-capture microdissection and examined by microarray-based gene expression analysis. Mononuclear cells (MNC) and airway epithelial cells (AECs) were isolated and stimulated with allergen, IL-1 beta, or IL-33 together with recombinant human (rh) IL-37. Wild-type, IL-1R1- and IL-33-deficient mice with EAA were treated with rhIL-37. IL-1 beta, IL-33, and IL-37 levels were determined in sputum and nasal secretions from adult asthma patients without glucocorticoid therapy. Results IL-37 target cells included AECs, T cells, and dendritic cells. In mice with EAA, rhIL-37 led to differential expression of >90 genes induced by IL-1 beta and IL-33. rhIL-37 reduced production of Th2 cytokines in allergen-activated MNCs from wild-type but not from IL-1R1-deficient mice and inhibited IL-33-induced Th2 cytokine release. Furthermore, rhIL-37 attenuated IL-1 beta- and IL-33-induced pro-inflammatory mediator expression in murine AEC cultures. In contrast to wild-type mice, hIL-37 had no effect on EAA in IL-1R1- or IL-33-deficient mice. We also observed that expression/production ratios of both IL-1 beta and IL-33 to IL-37 were dramatically increased in asthma patients compared to healthy controls. Conclusion IL-37 downregulates allergic airway inflammation by counterbalancing the disease-amplifying effects of IL-1 beta and IL-33.
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