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IL-37 alleviates house dust mite-induced chronic allergic asthma by targeting TSLP through the NF-κB and ERK1/2 signaling pathways.
- Source :
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Immunology and cell biology [Immunol Cell Biol] 2019 Apr; Vol. 97 (4), pp. 403-415. Date of Electronic Publication: 2019 Jan 23. - Publication Year :
- 2019
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Abstract
- Interleukin (IL)-37 has been described as a negative regulator of immune responses and is critical for asthma pathogenesis, but the mechanisms behind the protective role of IL-37 against allergic asthma are less well understood. We show here that IL-37 administered intranasally inhibited house dust mite (HDM)-induced chronic airway eosinophilic inflammation, goblet cell hyperplasia, peribronchial collagen deposition and airway hyperresponsiveness (AHR) to methacholine. In contrast to a weakened Th2 response in the lung that was characterized by the downregulation of Th2-associated cytokines and chemokines in IL-37-treated mice, IL-37 has no effect on relevant markers of systemic Th2 immune including serum immunoglobulins expression and in vitro production of Th2-associated cytokines by splenocytes on HDM recall. We demonstrated that the production of thymic stromal lymphopoietin (TSLP) in the lung tissue was associated with IL-37. Importantly, compared with IL-37 alone, TSLP coadministration with IL-37 restored HDM-induced airway inflammation and structural alterations, increased AHR to methacholine and promoted Th2-associated cytokine production. We further found that IL-37 inhibited the induction of TSLP expression by the main antigen of house dust mite, Der p1, by suppressing NF-κB and extracellular signal regulated kinase 1/2 (ERK1/2) activation in human bronchial epithelial (16-HBE) cells in vitro. These data highlight the importance of TSLP in IL-37-mediated protective role in asthma. IL-37 might represent a useful innovative and alternative therapy to control TSLP production in the airway.<br /> (© 2018 Australasian Society for Immunology Inc.)
- Subjects :
- Airway Remodeling drug effects
Animals
Asthma complications
Asthma immunology
Asthma physiopathology
Cell Line
Chronic Disease
Cytokines administration & dosage
Epithelial Cells drug effects
Epithelial Cells immunology
Epithelial Cells parasitology
Female
Humans
Hypersensitivity complications
Hypersensitivity immunology
Hypersensitivity physiopathology
Interleukin-1 pharmacology
Mice, Inbred BALB C
Pyroglyphidae drug effects
Respiratory Hypersensitivity complications
Respiratory Hypersensitivity immunology
Respiratory Hypersensitivity physiopathology
Th2 Cells drug effects
Th2 Cells immunology
Thymic Stromal Lymphopoietin
Asthma drug therapy
Cytokines metabolism
Hypersensitivity diet therapy
Interleukin-1 therapeutic use
MAP Kinase Signaling System drug effects
NF-kappa B metabolism
Pyroglyphidae physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1440-1711
- Volume :
- 97
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Immunology and cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 30537285
- Full Text :
- https://doi.org/10.1111/imcb.12223