# Intraepithelial lymphocyte regulation of epithelial cell shedding

> **NIH NIH R21** · RBHS-NEW JERSEY MEDICAL SCHOOL · 2020 · $193,062

## Abstract

PROJECT SUMMARY.
Maintenance of an intact intestinal barrier is critical to prevent microbial activation of mucosal
immunity. γδ intraepithelial lymphocytes (IEL) migrate extensively within the epithelial compartment to
serve as a first line of defense against luminal antigens and invasive enteric microbes. Although γδ
IELs can induce epithelial proliferation, whether γδ IELs regulate cell shedding has yet to be
investigated. Our preliminary data generated for this application demonstrate γδ IELs are required for
pathological cell shedding in response to systemic lipopolysaccharide (LPS) exposure; however, the
mechanisms regulating this process remain unclear. This proposal seeks to elucidate the role of γδ IEL
migratory behavior in pathological cell shedding and begin to define the molecular mechanisms by
which γδ IELs contribute to these shedding events. Specifically, we propose to investigate the
spatiotemporal dynamics of γδ IEL interactions with LPS-induced shedding events, the role of γδ IEL
motility in regulating shedding, and whether local γδ IEL secretion of granzyme into the extracellular
matrix facilitates release of enterocytes from the basement membrane as a critical component of the
shedding process. Using an integrated approach that combines cutting edge imaging technologies with
cell biology and immunological techniques, these studies will be the first to identify a direct role for γδ
IELs in the regulation of pathological cell shedding. These experiments will not only elucidate a novel
functional role for γδ IELs in the intestinal mucosa, but also provide the basis to investigate the extent
to which specific subsets of γδ IELs contribute to maintenance of the epithelial barrier as a potential
area of therapeutic development to aid in mucosal healing.

## Key facts

- **NIH application ID:** 9857554
- **Project number:** 5R21AI143892-02
- **Recipient organization:** RBHS-NEW JERSEY MEDICAL SCHOOL
- **Principal Investigator:** Karen Leigh Edelblum
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $193,062
- **Award type:** 5
- **Project period:** 2019-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857554

## Citation

> US National Institutes of Health, RePORTER application 9857554, Intraepithelial lymphocyte regulation of epithelial cell shedding (5R21AI143892-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9857554. Licensed CC0.

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