# Immune signaling molecules involved in promoting the pathogenesis of eosinophilic esophagitis (EoE)

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 2021 · $466,178

## Abstract

ABSTRACT
Eosinophilic esophagitis (EoE) is a chronic immune system disease. It has been identified only in the past two
decades, but is now considered a major cause of esophageal disorder in both pediatric and adult population.
The current proposal is the extension of our studies that provided novel findings including the role of IL-15
responsive iNKT cells, significance of IL-18 in IL-15 induced esophageal eosinophilia, the chemoattractant role
of nerve cells derived neuropeptide VIP in EoE, and most importantly we reported a critical role IL-18 to
transform IL-5 generated naïve eosinophils to CD274 expressed pathogenic eosinophils. The proposed
extended studies will now establish the physiological role of IL-18 and VIP in eosinophils and mast cells
accumulation and degranulation in and beyond the epithelial mucosa that promotes esophageal functional
abnormalities including motility dysfunction in chronic EoE. The mechanisms driving the eosinophil and mast cell
accumulation, activation and degranulation in the muscular mucosa is yet not fully understood. Notably, no
evidence indicates that muscle or neuronal cells are the sources of eotaxin-1, -2 or -3. Even after a decade of
reported highly induced eotaxin-3 and its correlation with esophageal eosinophilia, yet the direct physiological
significance of eotaxin--3 is not established in EoE. Therefore, it is critical to understand the role of tissue
specific IL-18 induction and the mechanisms operational in the trafficking and accumulation of IL-18 transformed
pathogenic eosinophils and mast cells in and beyond the epithelial mucosa. Our reports indicates that
eosinophils and mast cells accumulation promotes epithelial, subepithelial and muscular mucosa fibrosis,
muscle cell hyperplasia and esophageal functional abnormalities in human EoE. Most recently, we reported that
eosinophils accumulate adjacent to nerve cells and neuroendocrine cell-derived vasoactive intestinal peptide has
a chemoattractant role for eosinophils similar to the eotaxin(s). In addition, most recently both in vitro and in
vivo, we showed that VIP receptor antagonist restrict eosinophils motility. Therefore, our extended grant
studies will test the hypotheses that IL-18 and a neuroendocrine cell-derived chemoattractant
vasoactive intestinal peptide is critical for the maturation, activation, and accumulation of eosinophils
and mast cells in each segment of the esophagus and are the key for the development of fibrosis
associated strictures and motility dysfunction. Accordingly, we propose three specific aims to establish the
mechanistic pathways involved in IL-18-driven eosinophil and mast cell maturation, activation, and degranulation
in each segment of the esophageal mucosa (AIM I); tissue-specific IL-18 induction is critical in promoting EoE
pathogenesis (AIM II) and lastly, establish the role of neuroendocrine cell-derived vasoactive intestinal peptide in
eosinophil and mast cell accumulation and degranulation within the mu...

## Key facts

- **NIH application ID:** 10070570
- **Project number:** 5R01AI080581-11
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** ANIL MISHRA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $466,178
- **Award type:** 5
- **Project period:** 2009-07-22 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10070570

## Citation

> US National Institutes of Health, RePORTER application 10070570, Immune signaling molecules involved in promoting the pathogenesis of eosinophilic esophagitis (EoE) (5R01AI080581-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10070570. Licensed CC0.

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