Innate immune cell dysregulation drives inflammation and disease in aspirin-exacerbated respiratory disease

Ryan Eid, Carol H. Yan, Whitney Stevens, Taylor A. Doherty, Larry Borish*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

Aspirin-exacerbated respiratory disease (AERD) is a complex inflammatory disorder that is not generally viewed as a disease involving the adaptive immune system but instead one largely driven by the innate immune system. This article focuses on the cellular dysregulation involving 4 central cell types: eosinophils, basophils, mast cells, and innate lymphoid type 2 cells. AERD can be envisioned as involving a self-perpetuating vicious circle in which mediators produced by a differentiated activated epithelial layer, such as IL-25, IL-33, and thymic stromal lymphopoietin, engage and activate each of these innate immune cells. The activation of these innate immune cells with their production of additional cytokine/chemokine and lipid mediators leads to further recruitment and activation of these innate immune cells. More importantly, numerous mediators produced by these innate immune cells provoke the epithelium to induce further inflammation. This self-perpetuating cycle of inflammation partially explains both current interventions suggested to ameliorate AERD (eg, aspirin desensitization, leukotriene modifiers, anti–IL-5/IL-5 receptor, anti–IL-4 receptor, and anti-IgE) and invites exploration of novel targets as specific therapies for this condition (prostaglandin D2 antagonists or cytokine antagonists [IL-25, IL-33, thymic stromal lymphopoietin]). Several of these interventions currently show promise in small retrospective analyses but now require definite clinical trials.

Original languageEnglish (US)
Pages (from-to)309-318
Number of pages10
JournalJournal of Allergy and Clinical Immunology
Volume148
Issue number2
DOIs
StatePublished - Aug 2021

Keywords

  • Aspirin-exacerbated respiratory disease
  • IgE
  • basophils
  • eosinophils
  • innate lymphoid cells
  • mast cells
  • type 2 inflammation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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