IL-1RA regulates immunopathogenesis during fungal-Associated allergic airway inflammation

Academic Article

Abstract

  • © 2019 American Society for Clinical Investigation. All rights reserved. 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, 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.
  • Published In

  • JCI insight  Journal
  • Digital Object Identifier (doi)

    Author List

  • Godwin MS; Reeder KM; Garth JM; Blackburn JP; Jones MJ; Yu Z; Matalon S; Hastie AT; Meyers DA; Steele C
  • Volume

  • 4
  • Issue

  • 21