# Epithelial antigen presentation in regulation of the host-microbiota relationship

> **NIH NIH F32** · CINCINNATI CHILDRENS HOSP MED CTR · 2021 · $68,562

## Abstract

Project Summary
 Despite a clear link between intestinal immunity and the microbiota, the mechanisms regulating host immune
responses to commensal microbes remain poorly understood. Intestinal epithelial cells (IECs) reside at the direct
interface between the microbiota and dynamic immune cells and are thus uniquely poised to calibrate host
immunity. Although IECs are likely critical for deciphering harmful versus harmless antigens and instructing the
appropriate immune reaction, remarkably little is known about mechanisms that enable IECs to modulate host-
microbiota interactions. Antigen presenting cells (APCs) must differentiate between harmless and harmful
antigens and coordinate proper T cell responses. Although atypical APCs, my preliminary data demonstrate that
IECs are the most abundant MHCII-expressing cells in the intestine and that MHCII expression in IECs is directly
upregulated by microbiota. Thus, I hypothesize that epithelial antigen presentation may be essential for
mediating host-microbiota interactions that impact intestinal homeostasis and inflammation. Studies outlined in
this proposal will directly test this hypothesis by defining the function of IEC-intrinsic MHCII. Employing newly
developed mutant mouse strains, intestinal organoids, and established models of intestinal inflammation, two
specific aims are proposed that will determine (i) the influence of IEC-intrinsic MHCII expression on mucosal
barrier function and immune homeostasis and (ii) how IEC-intrinsic MHCII regulates development of intestinal
inflammation. Collectively, these studies will provide new insights into how microbiota direct intestinal immunity
and will guide novel approaches for investigating and treating intestinal inflammatory diseases.
 During my past research experiences, I discovered my strong interest in the host-microbiota relationship.
For this reason, I initiated the proposed project with Dr. Theresa Alenghat that will build upon my knowledge of
innate immunity and antigen presentation and enable me to transition into the field of mucosal immunology. My
thesis work provided me with an excellent foundation in host-pathogen interactions, microbiology, and
immunology, but I have not had previous exposure to epithelial regulation, antigen-specific techniques, and
intestinal disease models. The labs of my mentors, Dr. Alenghat and Dr. Sing Sing Way, along with the
exceptional scientific and intellectual environment at Cincinnati Children’s Hospital will enable me to utilize
modern, innovative approaches in my research and collaborate with top investigators. Over the next three years,
I fully anticipate that my background in conjunction with my current training plan will allow me to successfully
carry out the proposed project. The mentoring and training I will receive will enable me to successfully transition
to an independent research career that can address questions directed towards fundamental advances in
mucosal immunity, as well as innovative ...

## Key facts

- **NIH application ID:** 10118004
- **Project number:** 5F32AI147591-02
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Emily M. Eshleman
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $68,562
- **Award type:** 5
- **Project period:** 2020-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10118004

## Citation

> US National Institutes of Health, RePORTER application 10118004, Epithelial antigen presentation in regulation of the host-microbiota relationship (5F32AI147591-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10118004. Licensed CC0.

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