# Gamma delta IEL control of intestinal infection: roles for CD100 and JAML

> **NIH NIH R21** · SCRIPPS RESEARCH INSTITUTE, THE · 2020 · $241,875

## Abstract

Summary
Epithelial resident T cells that express the gd T cell receptor play a crucial role in maintaining
homeostasis at mucosal surfaces. This is particularly challenging in the intestine which is
constantly bathed with commensal microbes as well as ingested potentially pathogenic bacteria.
Disruption of this fine balance can lead to systemic infection. gd T cell receptor-expressing
intraepithelial lymphocytes (gd IEL) provide important protections against systemic infection,
however the molecular mechanisms driving their protective functions are not well characterized.
Crosstalk between gd T cells and their neighboring epithelial cells is vital to this process and
clues from the regulation of gd T cells in the epidermis have implicated CD100 and JAML as
important players. We propose that CD100 and JAML are crucial regulators of the gd IEL
response to intestinal infection and provide protections against bacterial translocation across the
epithelium and limit subsequent systemic infection. We will test this hypothesis through analysis
of gd IEL responses to Salmonella typhimurium infection in the presence or absence of CD100
and JAML. We will use congenic animals to add back CD100- or JAML-sufficient gd IEL to
demonstrate the specific requirement for these molecules on gd IEL in pathogen responses.
Information gained through these studies may demonstrate the potential for these molecules as
new targets for therapeutic strategies. Additionally the data obtained will provide insight into the
mechanisms of gd T cell responses to infection in other mucosal sites and will thus contribute to
our understanding of the molecular mechanisms governing mucosal immunity.

## Key facts

- **NIH application ID:** 9851343
- **Project number:** 5R21AI144825-02
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Deborah A Witherden
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $241,875
- **Award type:** 5
- **Project period:** 2019-01-18 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851343

## Citation

> US National Institutes of Health, RePORTER application 9851343, Gamma delta IEL control of intestinal infection: roles for CD100 and JAML (5R21AI144825-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9851343. Licensed CC0.

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