# The role of CD73 in esophageal epithelial homeostasis

> **NIH NIH R01** · CHILDREN'S HOSP OF PHILADELPHIA · 2024 · $757,364

## Abstract

PROJECT SUMMARY
Eosinophilic esophagitis (EoE) is a chronic, debilitating allergic disorder that is increasing in incidence worldwide,
resulting significant health care and financial burdens. Current therapeutic approaches in EoE include dietary
elimination and limiting inflammatory signaling using corticosteroids or biologics; however, there is increasing
recognition of an EoE patient population failing to exhibit clinical and histological remission in response to these
interventions. Disruption of esophageal epithelial tissue architecture and barrier function are hallmarks of EoE
and achieving healing of the esophageal epithelial barrier represents a significant clinical challenge. Our own
published work demonstrates that maintained epithelial remodeling is associated with symptoms in patients with
histologically inactive EoE. Moreover, a recent study demonstrated that epithelium of inactive EoE patients fails
to normalize at the cellular and molecular level. Despite the importance of esophageal epithelium in EoE
pathobiology, we lack the comprehensive understanding of the mechanisms regulating esophageal epithelial
homeostasis that is necessary to shape approaches for promoting epithelial healing in EoE. In a recent
publication, we identified a CD73+ progenitor population within the basal zone of esophageal epithelium that is
critical for tissue renewal. We further found that CD73+ basal cells are depleted in human subjects and mice
with EoE inflammation, with the EoE-associated cytokines IL-4 and IL-13 causing a shift from CD73+ to CD73-
basal cells in human 3D organoids. CD73 is a membrane-bound ectoenzyme that catalyzes conversion of
extracellular adenosine monophosphate into the purine nucleoside adenosine. In the current proposal, we
provide robust preliminary data adenosine (1) restores organoid formation, differentiation, and barrier integrity in
esophageal keratinocytes with genetic depletion of CD73; and (2) improves epithelial differentiation in IL-13-
treated organoids and a mouse model of EoE. Based upon our published and preliminary data, we hypothesize
that esophageal homeostasis is mediated by CD73+ epithelial cells and dysregulated purinergic signaling
contributes to EoE pathobiology, including epithelial remodeling. We will test this hypothesis by: defining the
direct requirement of squamous epithelial CD73 in esophageal homeostasis and response to EoE (Aim 1);
identifying the molecular mechanisms through which adenosine signaling supports esophageal epithelial
homeostasis (Aim 2); and delineating how levels of CD73 and CD73-associated purines relate to clinical features
of EoE patients (Aim 3). This proposal will illuminate the functional and mechanistic roles of CD73 and purinergic
signaling in esophageal homeostasis. The proposed studies will also assess the therapeutic utility of restoring
purinergic signaling in EoE models and the clinical significance of alterations in CD73 and purines in EoE
patients, which may have imp...

## Key facts

- **NIH application ID:** 10998275
- **Project number:** 1R01DK138634-01A1
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Amanda Brooke Muir
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $757,364
- **Award type:** 1
- **Project period:** 2024-09-16 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10998275

## Citation

> US National Institutes of Health, RePORTER application 10998275, The role of CD73 in esophageal epithelial homeostasis (1R01DK138634-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10998275. Licensed CC0.

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