IL-1RA regulates immunopathogenesis during fungal-associated allergic airway inflammation
AuthorGodwin, Matthew S
Reeder, Kristen M
Garth, Jaleesa M
Blackburn, Jonathan P
Hastie, Annette T
Meyers, Deborah A
AffiliationUniv Arizona, Dept Med
MetadataShow full item record
PublisherAMER SOC CLINICAL INVESTIGATION INC
CitationJCI Insight. 2019; 4(21): e129055. https://doi.org/10.1172/jci.insight.129055.
RightsCopyright © 2019, American Society for Clinical Investigation.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractSevere 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.
VersionFinal published version
SponsorsUnited States Public Health Service [HL109164, HL122426, HL136211]
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