A65 THE YAP-PER: CAN YAP/TAZ MEDIATE EPITHELIAL-IMMUNE CROSSTALK DURING PYLORIC METAPLASIA?

TL;DR

This study explores how YAP/TAZ proteins influence immune responses and tissue regeneration in the stomach during infection and injury.

Contribution

The study investigates the role of YAP/TAZ in epithelial-immune crosstalk during pyloric metaplasia and H. pylori infection.

Findings

Loss of YAP/TAZ leads to chronic B cell infiltration after tissue injury.

YAP/TAZ deletion results in differential type II immune responses in gastric tissue.

YAP/TAZ may regulate immune responses during both injury and H. pylori infection.

Abstract

Gastric cancer is one of the leading causes of cancer-related deaths and its prevalence has been associated with infection by Helicobacter pylori. H. pylori persistence leads to chronic inflammation, which results in the elimination of acid-secreting parietal cells and the appearance of abnormal mucus-producing cells at the base of the gastric glands, known as spasmolytic polypeptide/trefoil factor 2-expressing metaplasia (SPEM) cells. The processes driving these alterations in epithelial cell fate during H. pylori infection and their function in regeneration of the gastric epithelium remain unclear. Previous work done in our lab have demonstrated that Hippo signalling, more specifically the transcriptional effectors yes-associated protein 1 (YAP) and transcription coactivator with PDZ-binding motif (TAZ), plays an essential role in controlling cell fate during gastric tissue regeneration in a chemical injury model. In the same model, loss of YAP/TAZ resulted in chronic immune cell infiltration in corpus glands, suggesting an immunomodulatory role for YAP and TAZ.

The objectives of this project is to characterize the immunomodulatory function of YAP/TAZ in an in vivo model of acute injury as well as an in vivo model of H. pylori infection.

Acute injury is induced by high-dose tamoxifen treatment in conditional knock-out (cKO) mice with YAP/TAZ deleted throughout the gastric epithelium. Subsequent immunophenotyping experiments such as flow cytometry and multiplex analysis are performed to characterize the role played by YAP/TAZ in regulating the immune response. For a more biologically relevant model, cKO mice are also infected with H. pylori, and similar immunophenotyping analyses are performed.

Preliminary results showed that the loss of YAP/TAZ resulted in differential type II response as well as chronic B cell infiltration upon tissue injury.

This project aims to provide important insights on immune-epithelial cell interactions important for tissue regeneration and tumorigenesis as well as host-pathogen interactions implicated in H. pylori persistence.

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