# Basal Progenitor Cells and Eosinophilic Esophagitis

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $392,247

## Abstract

ABSTRACT
Eosinophilic esophagitis (EoE) is a recently characterized disease that has been rising dramatically over the
past decade. It affects people of all ages with a preference in children and adults in their 30-40’s. EoE
pathogenesis has been associated with allergen/immune reactions with characterized high levels of cytokines
including IL-13. Prolonged inflammation results in tissue remodeling including hyperplasia of basal progenitor
cells, subepithelial fibrosis and stricture of the esophagus. Although common topical corticosteroid therapy
improves the clinicopathologic features in most patients, EoE almost always recurs when steroids are
discontinued. Therefore, a better understanding of the pathobiology of this disease is necessitated for deriving
novel effective treatment. We and others have previously shown that IL-13 plays a critical role in the initiation
of EoE and subsequent tissue remodeling. However, the molecular mechanism by which IL-13 regulates basal
progenitor cells remains largely unexplored. To address this issue we recently performed a comprehensive
analysis of IL13-stimulated secretome, and identified that the 250kD isoform of Tenascin C (TNC250) is
enriched in IL13-treated human esophageal basal cells, mouse and human EoE biopsies. Our preliminary data
further show that knockdown of the transcripts encoding TNC250 leads to reduced proliferation of basal
progenitor cells accompanied by decreased levels of TNFR-associated factors (TRAF)3 which is an E3
ubiquitin Ligase for MAP3K14 (also known as NF-kappa-B-inducing kinase (Nik)). Significantly, deletion of Nik
leads to EoE with prominent basal cell hyperplasia and eosinophil infiltration. Our preliminary data further
suggest that loss of Nik in the esophagus but not other tissues (e.g. thymus and hematopoietic system) is
critical for EoE pathogenesis. Our hypothesis is that IL-13/TNC250 inhibits Nik-mediated non-canonical
NF-κB signaling in the esophageal epithelium to promote EoE pathogenesis. We will test our hypothesis
with the following specific aims: (Aim1) To test the hypothesis that TNC250 downstream of IL-13 promotes
basal cell hyperplasia during EoE pathogenesis. (Aim2) To determine the role of Nik in EoE pathogenesis,
which include two subaims: (Aim2a) To test the hypothesis that loss of Nik expression in the esophageal
epithelium promotes EoE pathogenesis. (Aim2b) To test the hypothesis that loss of Nik promotes EoE through
non-canonical NF-kB signaling. This project is expected to provide novel genetic and molecular mechanisms
regulating basal progenitor cells. The insights gained through studying NF-kB signaling in EoE animal models
will lay an important foundation for translating these findings into the clinic.

## Key facts

- **NIH application ID:** 9859386
- **Project number:** 5R01DK100342-08
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Jianwen Que
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $392,247
- **Award type:** 5
- **Project period:** 2014-04-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9859386

## Citation

> US National Institutes of Health, RePORTER application 9859386, Basal Progenitor Cells and Eosinophilic Esophagitis (5R01DK100342-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9859386. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*