Active eosinophilic esophagitis is characterized by epithelial barrier defects and eosinophil extracellular trap formation.

Simon, Dagmar; Radonjic, Susanne Irene; Straumann, A; Yousefi, Shida; Simon, Hans-Uwe (2015). Active eosinophilic esophagitis is characterized by epithelial barrier defects and eosinophil extracellular trap formation. Allergy, 70(4), pp. 443-452. Wiley-Blackwell 10.1111/all.12570

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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). CONCLUSION 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology

UniBE Contributor:

Simon, Dagmar; Radonjic, Susanne Irene; Yousefi, Shida and Simon, Hans-Uwe

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0105-4538

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Debora Scherrer

Date Deposited:

23 Jul 2015 16:16

Last Modified:

12 Sep 2017 02:47

Publisher DOI:

10.1111/all.12570

PubMed ID:

25620273

Uncontrolled Keywords:

antimicrobial peptides; eosinophil extracellular traps; eosinophilic esophagitis; eosinophils; epithelial barrier

BORIS DOI:

10.7892/boris.70452

URI:

https://boris.unibe.ch/id/eprint/70452

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