# Microbiota-gamma delta IEL-Paneth cell axis in host antimicrobial response

> **NIH NIH R21** · RBHS-NEW JERSEY MEDICAL SCHOOL · 2022 · $228,017

## Abstract

PROJECT SUMMARY.
Maintenance of an intact intestinal barrier is critical to prevent microbial activation of mucosal
immunity. gd intraepithelial lymphocytes (IEL) migrate extensively within the epithelial compartment to
serve as a first line of defense against luminal antigens and invasive enteric microbes, and have been
implicating in regulating Paneth cell secretion of antimicrobial peptides. Although microbial-derived
molecules contribute to gd IEL homeostasis, specific commensal bacteria have yet to be associated
with alterations in gd IEL number and/or function. Moreover, the extent to which gd IEL-mediated
signaling influences Paneth cell function has yet to be explored. In preliminary data generated for this
application, we identified 5 amplicon sequence variants (ASV) that are strongly associated with the
expansion of gd IELs under homeostatic conditions. We also show that epithelial cells isolated from WT
mice with an expanded gd IEL compartment also exhibit a significant upregulation of genes involved in
Paneth cell antimicrobial peptide production and secretion. Therefore, this proposal seeks to identify
the contribution of individual commensals to the expansion of the gd IEL compartment and determine
the extent of gd IEL-Paneth cell crosstalk in WT mice exhibiting this hyperproliferative phenotype.
Using an integrated approach that combines unique mouse models and cutting edge imaging
technologies both in vitro and in vivo, these studies will be the first to identify the contribution of
individual commensals in the amplification of gd IEL proliferation and surveillance behavior, and
elucidate whether gd IELs directly promote Paneth cell function. Developing a better understanding of
the microbiota-gd IEL-Paneth cell axis may identify novel therapeutic targets to aid in host defense and
help maintain remission in Crohn’s disease patients.

## Key facts

- **NIH application ID:** 10520149
- **Project number:** 1R21AI171959-01
- **Recipient organization:** RBHS-NEW JERSEY MEDICAL SCHOOL
- **Principal Investigator:** Karen Leigh Edelblum
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $228,017
- **Award type:** 1
- **Project period:** 2022-06-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10520149

## Citation

> US National Institutes of Health, RePORTER application 10520149, Microbiota-gamma delta IEL-Paneth cell axis in host antimicrobial response (1R21AI171959-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10520149. Licensed CC0.

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