title: Active eosinophilic esophagitis is characterized by epithelial barrier defects and eosinophil extracellular trap formation.
abstract: BACKGROUND
  Eosinophilic esophagitis (EoE) exhibits esophageal dysfunction owing to an eosinophil-predominant inflammation. Activated eosinophils generate eosinophil extracellular traps (EETs) able to kill bacteria. There is evidence of an impaired barrier function in EoE that might allow pathogens to invade the esophagus. This study aimed to investigate the presence and distribution of EETs in esophageal tissues from EoE patients and their association with possible epithelial barrier defects.
  
  
  METHODS
  Anonymized tissue samples from 18 patients with active EoE were analyzed. The presence of DNA nets associated with eosinophil granule proteins forming EETs and the expression of filaggrin, the protease inhibitor lympho-epithelial Kazal-type-related inhibitor (LEKTI), antimicrobial peptides, and cytokines were evaluated by confocal microscopy following immune fluorescence staining techniques.
  
  
  RESULTS
  Eosinophil extracellular trap formation occurred frequently and was detected in all EoE samples correlating with the numbers of infiltrating eosinophils. While the expression of both filaggrin and LEKTI was reduced, epithelial antimicrobial peptides (human beta-defensin-2, human beta-defensin-3, cathelicidin LL-37, psoriasin) and cytokines (TSLP, IL-25, IL-32, IL-33) were elevated in EoE as compared to normal esophageal tissues. There was a significant correlation between EET formation and TSLP expression (P = 0.02) as well as psoriasin expression (P = 0.016). On the other hand, a significant negative correlation was found between EET formation and LEKTI expression (P = 0.016).
  
  
  CONCLUSIONS
  Active EoE exhibits the presence of EETs. Indications of epithelial barrier defects in association with epithelial cytokines are also present which may have contributed to the activation of eosinophils. The formation of EETs could serve as a firewall against the invasion of pathogens.
authors.affiliation: Department of Dermatology, Inselspital, Bern University Hospital, Bern, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Simon
authors.forename: S
authors.initials: S
authors.lastname: Radonjic-Hösli
authors.forename: A
authors.initials: A
authors.lastname: Straumann
authors.forename: S
authors.initials: S
authors.lastname: Yousefi
authors.forename: H-U
authors.initials: HU
authors.lastname: Simon
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism; D001706:Biopsy; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D057765:Eosinophilic Esophagitis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D065206:Extracellular Traps / Q000378:metabolism*; D000091344:Filaggrin Proteins; D005753:Gastric Mucosa / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D006801:Humans
chemical_list: D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; C000717249:FLG protein, human; D000091344:Filaggrin Proteins
keywords: antimicrobial peptides; eosinophil extracellular traps; eosinophilic esophagitis; eosinophils; epithelial barrier