Active eosinophilic esophagitis is characterized by epithelial barrier defects and eosinophil extracellular trap formation.
Simon. D D; Radonjic-Hösli. S S; Straumann. A A; Yousefi. S S; Simon. H-U HU
Key Findings
- Eosinophil extracellular traps (EETs) were found in every EoE tissue sample and matched the number of eosinophils present.
- Barrier proteins filaggrin and LEKTI were reduced, indicating a compromised epithelial barrier.
- Antimicrobial peptides such as LL‑37, beta‑defensins, and psoriasin were elevated in the diseased tissue.
- EET formation correlated positively with cytokines like TSLP and negatively with LEKTI expression.
Practical Outcomes
- The study shows that LL‑37 rises naturally during esophageal inflammation, but it does not suggest that taking LL‑37 supplements will help. For biohackers, the main takeaway is that boosting LL‑37 alone is unlikely to fix barrier defects; focusing on overall barrier health and controlling eosinophil activation may be more relevant.
Summary
In people with active eosinophilic esophagitis, immune cells called eosinophils release DNA nets (EETs) that trap microbes. The tissue shows weaker barrier proteins (filaggrin, LEKTI) and higher levels of natural antimicrobial peptides, including LL‑37. The amount of EETs is linked to certain inflammation signals but not directly to LL‑37 levels.
Abstract
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. 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. 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). 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.
Study Information
pubmed
2015
2015-01-26T00:00:00.000Z
10.1111/all.12570
119
57