title: Group 2 innate lymphoid cells are recruited to the nasal mucosa in patients with aspirin-exacerbated respiratory disease.
abstract: BACKGROUND
  Aspirin-exacerbated respiratory disease (AERD) is characterized by tissue eosinophilia and mast cell activation, including abundant production of prostaglandin D2(PGD2). Group 2 innate lymphoid cells (ILC2s), which promote tissue eosinophilia and mast cell responses, undergo chemotaxis and cytokine production in response to PGD2, but it is unknown whether ILC2s are active in patients with AERD.
  
  
  OBJECTIVE
  We sought to determine whether ILC2 numbers change in peripheral blood and the nasal mucosa during COX-1 inhibitor-induced reactions in patients with AERD.
  
  
  METHODS
  Blood and nasal scrapings were collected at baseline, during reactions, and after completion of ketorolac/aspirin challenge/desensitization in 12 patients with AERD. ILC2s and eosinophils were quantitated by means of flow cytometry. Urine was also collected, and quantification of PGD2metabolite and leukotriene E4levels was done by using ELISA. Baseline and nonsteroidal anti-inflammatory drug reaction clinical data were correlated with cell changes.
  
  
  RESULTS
  ILC2 numbers significantly increased in nasal mucosal samples and decreased in blood at the time of COX-1 inhibitor reactions in 12 patients with AERD. These changes were not observed in 2 patients without AERD. Furthermore, eosinophil numbers decreased in blood concurrently with significant increases in urinary PGD2metabolite and leukotriene E4levels. The magnitude of increases in nasal mucosal ILC2 numbers positively correlated with maximum symptom scores during challenges. Furthermore, blood ILC2 numbers during the reaction correlated with time for the reaction to resolve, possibly reflecting reaction severity.
  
  
  CONCLUSIONS
  ILC2s are recruited to the nasal mucosa during COX-1 inhibitor-induced reactions in patients with AERD, correlating with enhanced production of prostaglandins and leukotrienes.
authors.affiliation: Department of Medicine, University of California, San Diego, Calif.
authors.forename: Jacqueline J
authors.initials: JJ
authors.lastname: Eastman
authors.affiliation: Department of Medicine, University of California, San Diego, Calif.
authors.forename: Kellen J
authors.initials: KJ
authors.lastname: Cavagnero
authors.affiliation: Department of Surgery, University of California-San Diego, La Jolla, Calif.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Deconde
authors.affiliation: Department of Medicine, University of California, San Diego, Calif.
authors.forename: Alex S
authors.initials: AS
authors.lastname: Kim
authors.affiliation: Department of Medicine, University of California, San Diego, Calif.
authors.forename: Maya R
authors.initials: MR
authors.lastname: Karta
authors.affiliation: Department of Medicine, University of California, San Diego, Calif.
authors.forename: David H
authors.initials: DH
authors.lastname: Broide
authors.affiliation: Department of Medicine, University of California, San Diego, Calif.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Zuraw
authors.affiliation: Division of Allergy, Asthma and Immunology, Scripps Clinic, La Jolla, Calif.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: White
authors.affiliation: Department of Medicine, University of California, San Diego, Calif.
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Christiansen
authors.affiliation: Department of Medicine, University of California, San Diego, Calif. Electronic address: tdoherty@ucsd.edu.
authors.forename: Taylor A
authors.initials: TA
authors.lastname: Doherty
mesh_terms: D000328:Adult; D000368:Aged; D055963:Asthma, Aspirin-Induced / Q000097:blood / Q000276:immunology* / Q000652:urine; D002452:Cell Count; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D003888:Desensitization, Immunologic; D015237:Dinoprost / Q000652:urine; D005260:Female; D006801:Humans; D020910:Ketorolac / Q000008:administration & dosage; D017999:Leukotriene E4 / Q000652:urine; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000166:cytology / Q000276:immunology*
chemical_list: D016861:Cyclooxygenase Inhibitors; D017999:Leukotriene E4; D015237:Dinoprost; D020910:Ketorolac
keywords: Group 2 innate lymphoid cells; aspirin-exacerbated respiratory disease