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IL-37 regulates allergic inflammation by counterbalancing pro-inflammatory IL-1 and IL-33
- Source :
- Allergy, DOI: 10.1111/all.15072 (2022)
- Publication Year :
- 2022
- Publisher :
- Wiley, 2022.
-
Abstract
- 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-1β, 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-1β, 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-1β 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-1β- 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-1β 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-1β and IL-33.
- Subjects :
- Immunology
Inflammation
medicine.disease_cause
Peripheral blood mononuclear cell
Allergic inflammation
Mice
Allergen
Th2 Cells
Asthma
Asthma Treatment
Interleukin
Gene expression
medicine
Immunology and Allergy
Animals
Humans
Lung
business.industry
Allergens
medicine.disease
Interleukin-33
Interleukin 33
Disease Models, Animal
Cytokines
medicine.symptom
business
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Allergy, DOI: 10.1111/all.15072 (2022)
- Accession number :
- edsair.doi.dedup.....214fd0d3d79d3294ccdae3bb5fd5e796