# Project-002

> **NIH NIH U19** · CINCINNATI CHILDRENS HOSP MED CTR · 2020 · $318,307

## Abstract

Epithelial cells are uniquely positioned as the very first line of defense to recognize type-2 (Th2)-cell-mediated
immune insults such as highly allergenic foods, proteolytic allergens and parasites. Herein, we focus on an
endogenous pathway that normally curtails the development of Th2 immunity at the squamous mucosa
mediated by the serine protease inhibitor SPINK7, whose loss of function is involved in unleashing marked Th2
related responses. We will focus on the prototypic human allergic disease, eosinophilic esophagitis (EoE), a
chronic, food-driven, tissue-specific, esophageal, inflammatory allergic disease characterized by marked
mucosal eosinophil accumulation and IBF mediated by loss of desmoglein (dsg)-1, not only because of the
urgent need to uncover a better understanding of this emerging unmet disease, but also because it provides
unique opportunities to examine mechanisms of tissue specificity and cross talk with other allergic diseases
(e.g. atopic dermatitis [AD] and asthma), which are being studied throughout this Center Grant. Consistent with
the theme of this Center Grant, EoE is a persistent disease of childhood that often progresses into fibrostenotic
complications and likely other atopic diseases. This Project 2 of the Center Grant aligns with the central theme
of uncovering mechanism for the induction of allergic disease and its persistence and interplay with the
development of other allergic diseases. We aim to test our central hypothesis is that decreased expression of
SPINK7 in esophageal epithelium promotes EoE by unleashing a protease dependent pro-inflammatory
response accompanied by IBF and TSLP production. This hypothesis will be tested in Aim 1, focused on
determining the role of SPINK7 in regulating epithelial cell function; Aim 2, focused on the role of SPINK7
regulation of the key pro-Th2 cytokine TSLP; and Aim 3 focused on elucidating the transcriptional regulation
and genetic contribution of SPINK7. Collectively, we aim to prove that SPINK7 has an essential role as a key
innate checkpoint in the esophageal epithelium and its loss promotes EoE.

## Key facts

- **NIH application ID:** 10226688
- **Project number:** 5U19AI070235-15
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Gurjit K. Khurana Hershey
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $318,307
- **Award type:** 5
- **Project period:** 2006-07-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10226688

## Citation

> US National Institutes of Health, RePORTER application 10226688, Project-002 (5U19AI070235-15). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10226688. Licensed CC0.

---

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