# Innate and adaptive immunity in celiac disease

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2023 · $547,301

## Abstract

PROJECT SUMMARY
Celiac disease (CeD), a complex T cell-mediated enteropathy induced by dietary gluten in HLA-DQ2 or HLA-
DQ8 individuals, currently affects 1% of the global population. While CD4 T cells are required for the
development of villus atrophy (VA), the effector cells mediating intestinal epithelial cell destruction (IEC) are
intraepithelial cytotoxic lymphocytes (IE-CTLS). Currently, the only effective CeD treatment is a lifelong gluten-
free diet (GFD). However, 30-40% of adult CeD patients fail to restore a completely normal intestinal
morphology on a GFD, and complete avoidance of gluten can be challenging. During the last funding period,
we generated the first HLA and gluten-dependent mouse model of CeD (CeD-tg) that recapitulates the
intricacies of CeD pathogenesis. We will take advantage of the CeD-tg mouse model and our expertise in
human immunology, to (i) further dissect the mechanisms underlying tissue destruction, and (ii) profile the
clinical spectrum of CeD using high dimensional single cell technologies with the goal of identifying new
therapeutic avenues and biomarkers predicting tissue destruction. The central hypothesis emerging from our
studies is that IE-CTL integrate signals from CD4 T cells and IEC to become licensed killer cells and mediate
tissue destruction. Furthermore, while it is acknowledged that IEC play a role in IE-CTL activation, their role in
CeD pathogenesis and how they impact on IE-CTL activation has not been investigated. The proposed specific
aims are:1) Establish the role of epithelial cells in T cell-mediated CeD immunopathology using the CeD Tg
mouse model; 2) Establish the Impact of γδ and CD4 T cells, IFNγ, IL-15 on IE-CTL activation in CeD-tg mice;
and 3) Profile the heterogeneity of potential and active CeD. The goal is to provide a knowledge base that will
help identify appropriate treatment strategies to individual patients, and help predict which potential CeD
patients (patients who have develop inflammatory anti-gluten immunity but conserve a normal intestinal
architecture) are at high risk of developing VA. The studies proposed will have a significant positive impact on
human health because they will help define curative and preventive strategies that have the potential to
prevent tissue destruction in celiac disease.

## Key facts

- **NIH application ID:** 10685629
- **Project number:** 5R01DK067180-19
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** BANA JABRI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $547,301
- **Award type:** 5
- **Project period:** 2005-09-09 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10685629

## Citation

> US National Institutes of Health, RePORTER application 10685629, Innate and adaptive immunity in celiac disease (5R01DK067180-19). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10685629. Licensed CC0.

---

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