Introduction 

This study, published in the European Journal of Allergy And Clinical Immunology, investigates eosinophilic oesophagitis (EoE), a chronic allergic disease characterised by oesophageal inflammation driven by cytokines IL-4 and IL-13.

This research holds significant relevance for patients suffering from EoE, offering valuable insights into the underlying mechanisms of the disease and paving the way for improved therapeutic approaches and better patient care.

Background 

Eosinophilic oesophagitis (EoE) is a chronic allergic disease characterised by inflammation in the oesophagus. It is driven by specific proteins called cytokines, specifically IL-4 and IL-13, which cause changes in the oesophageal lining. 

Dupilumab, a human antibody drug recently approved for use in the USA and EU, treats EoE by blocking the shared receptor component (IL-4Rα). However, it is unclear how much each cytokine contributes to the disease and whether IL-4Rα is involved. 

Methods

This study induced EoE in mice through skin sensitisation and intra-oesophageal challenges. RNA was extracted, sequenced for transcriptome analysis, and compared with human EoE RNAseq data.

Results

Mice lacking IL-13 receptor alpha 1 (IL-13Rα1) and mice with targeted IL-13 receptor alpha 1 deletion in oesophageal epithelial cells were protected from EoE symptoms. 

The study also found that IL-13Rα1 is mainly expressed in epithelial cells in human EoE biopsies, and genes associated with EoE were more strongly correlated with IL-13 expression than IL-4.

Conclusions

These findings demonstrate the importance of IL-13 signalling through IL-13Rα1 in EoE. It provides insights into the mechanisms of current EoE therapies and suggests that the type II IL-4 receptor could be a potential target for future treatments.

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