# The Role of Intestinal Epithelial Cells in the Generation of Protective CD4 Cytotoxic T Lymphocytes

> **NIH NIH F31** · LA JOLLA INSTITUTE FOR IMMUNOLOGY · 2020 · $39,934

## Abstract

PROJECT SUMMARY/ABSTRACT
CD4 cytotoxic T lymphocytes (CTL) accumulate in the small intestinal epithelium during steady state, but their
development and purpose(s) at this barrier are largely unknown. The unique localization of CD4 CTL to the small
intestinal epithelium suggests tissue-specific properties that direct CD4 CTL to develop from naive CD4 T helper
(Th) cells.
Similar to traditional myeloid antigen-presenting cells, intestinal epithelial cells (IECs) express MHC class II
(MHCII), suggesting a possible influence over nearby CD4 T cells. In addition, IECs are constantly processing
luminal contents and are expected to present tolerized antigens (e.g. diet or commensal bacteria-derived) to
CD4 T cells at its baso-lateral side. I have generated preliminary evidence that MHCII-processing of dietary
antigens by IECs is involved in the accumulation of CD4 CTL in the small intestinal epithelium.
Building on this finding, I hypothesize that the epithelium has a direct role in regulating CD4 Th cell conversion
into CD4 CTL. This resulting CD4 CTL population is further predicted to have a non-redundant protective role
against foodborne pathogens. Taken together, the presence of epithelial CD4 CTL could represent an immune
strategy that simultaneously adds an arm of defense while providing an alternative form of immunoregulation.
The proposed studies are expected to yield novel insights on mucosal CD4 T cell immunology that could be
relevant for the prevention or treatment of gastrointestinal diseases as well as improving vaccine development
strategies.
I propose to use a combination of conditional knock-out mouse models and a Salmonella pathogen model
analyzed with state-of-the-art flow cytometry, next-generation sequencing, and high-resolution microscopy to
determine the role of IECs as Ag-presenting cells in reprogramming CD4 Th cells into CD4 CTL and the
functional roles of these CD4 CTL during steady state or during infection. All experiments will be performed at
La Jolla Institute for Immunology, a leader in biomedical science research, under the guidance of sponsor Dr.
Hilde Cheroutre and co-sponsor Dr. Mitchell Kronenberg. In addition, I will receive professional guidance and
support from my collaborators and thesis committee in performing the studies. My growth as a scientist will also
be supplemented with classes and events held through the Biomedical Sciences PhD program at UC San Diego.
In summary, the proposed studies and training objectives of this F31 award application are geared towards
training me as to become a versatile independent researcher with a specialty in mucosal immunology and strong
scientific acumen.

## Key facts

- **NIH application ID:** 9993097
- **Project number:** 1F31DK124078-01A1
- **Recipient organization:** LA JOLLA INSTITUTE FOR IMMUNOLOGY
- **Principal Investigator:** Angeline Chen
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $39,934
- **Award type:** 1
- **Project period:** 2020-03-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993097

## Citation

> US National Institutes of Health, RePORTER application 9993097, The Role of Intestinal Epithelial Cells in the Generation of Protective CD4 Cytotoxic T Lymphocytes (1F31DK124078-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9993097. Licensed CC0.

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