IL-1RA regulates immunopathogenesis during fungal-associated allergic airway inflammation
| Autor: | Deborah A. Meyers, Matthew S. Godwin, Annette T. Hastie, Chad Steele, Sadis Matalon, Jonathan P. Blackburn, Zhihong Yu, Jaleesa M. Garth, MaryJane Jones, Kristen M. Reeder |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Allergy Interleukin-1beta Atopy Mice 03 medical and health sciences 0302 clinical medicine Interleukin-1alpha Hypersensitivity medicine Animals Humans Asthma Anakinra medicine.diagnostic_test business.industry Fungi Sputum General Medicine medicine.disease respiratory tract diseases Mice Inbred C57BL Interleukin 1 Receptor Antagonist Protein 030104 developmental biology Bronchoalveolar lavage Bronchial hyperresponsiveness 030220 oncology & carcinogenesis Immunology Female Methacholine Bronchial Hyperreactivity medicine.symptom business Bronchoalveolar Lavage Fluid Signal Transduction Research Article medicine.drug |
| Zdroj: | JCI Insight. 4 |
| ISSN: | 2379-3708 |
| DOI: | 10.1172/jci.insight.129055 |
| Popis: | Severe asthma with fungal sensitization (SAFS) defines a subset of human asthmatics with allergy to 1 or more fungal species and difficult-to-control asthma. We have previously reported that human asthmatics sensitized to fungi have worse lung function and a higher degree of atopy, which was associated with higher IL-1 receptor antagonist (IL-1RA) levels in bronchoalveolar lavage fluid. IL-1RA further demonstrated a significant negative association with bronchial hyperresponsiveness to methacholine. Here, we show that IL-1α and IL-1β are elevated in both bronchoalveolar lavage fluid and sputum from human asthmatics sensitized to fungi, implicating an association with IL-1α, IL-1β, or IL-1RA in fungal asthma severity. In an experimental model of fungal-associated allergic airway inflammation, we demonstrate that IL-1R1 signaling promotes type 1 (IFN-γ, CXCL9, CXCL10) and type 17 (IL-17A, IL-22) responses that were associated with neutrophilic inflammation and increased airway hyperreactivity. Each of these were exacerbated in the absence of IL-1RA. Administration of human recombinant IL-1RA (Kineret/anakinra) during fungal-associated allergic airway inflammation improved airway hyperreactivity and lowered type 1 and type 17 responses. Taken together, these data suggest that IL-1R1 signaling contributes to fungal asthma severity via immunopathogenic type 1 and type 17 responses and can be targeted for improving allergic asthma severity. |
| Databáze: | OpenAIRE |
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