# Innate immune cell regulation of metaplasia in the stomach

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2020 · $6,885

## Abstract

Project Summary
Globally, gastric cancer is a major health burden and remains one of the leading causes of cancer-related
death. As is true of several cancer types, gastric cancer development is often preceded by the emergence of
preneoplastic lesions. In gastric carcinogenesis, Helicobacter pylori-induced oxyntic atrophy causes chronic
inflammation and histopathologic changes that lead to metaplasia and then cancer in the gastric mucosa.
Identifying the events that promote metaplasia development in the stomach remains a priority, as identification
of any of these factors could lead to better surveillance methods and therapies. Our previous work in mouse
models of acute oxyntic atrophy have shown that metaplasia in the stomach develops in the setting of a type II
immune response, including production of type II cytokines, eosinophil infiltration, and alternatively activated
macrophages. In particular, we have shown that mice lacking Interleukin-13 (IL-13) fail to develop metaplasia
following oxyntic atrophy. It is clear that IL-13 plays an important role in the development of metaplasia,
however the source of IL-13 remains unknown. Type II innate lymphoid cells (ILC2s) have recently emerged as
important effector cells capable of producing robust levels of IL-13. ILC2s are a main contributor of IL-13 in the
gastrointestinal tract. I hypothesize that ILC2s are required for the development of metaplasia in the stomach
because they produce IL-13, which promotes chief cell transdifferentiation. To address this hypothesis, I will
pursue three specific aims. First, I will characterize tissue resident ILC2s found in the normal and metaplastic
gastric mucosa using single cell RNA sequencing and primary culture systems. Second, I will determine the
effects of depleting ILC2s in mouse models of acute oxyntic atrophy and metaplasia. Finally, I will determine if
IL-13 directly promotes chief cell transdifferentiation using a previously characterized conditionally-
immortalized chief cell culture system. Overall, these investigations could link the pathological progression of
metaplasia in the stomach to other type II mediated diseases and provide preclinical insights that may lead to
novel approaches to alter metaplasia development.

## Key facts

- **NIH application ID:** 9938576
- **Project number:** 5F31DK117592-03
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Anne R. Meyer
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $6,885
- **Award type:** 5
- **Project period:** 2018-07-01 → 2020-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9938576

## Citation

> US National Institutes of Health, RePORTER application 9938576, Innate immune cell regulation of metaplasia in the stomach (5F31DK117592-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9938576. Licensed CC0.

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