# Role of MAIT cells in a mouse model of spontaneous colitis

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2022 · $194,375

## Abstract

Project Summary. Inflammatory bowel diseases (IBD) are chronic and cause significant morbidity. An
estimated 3 million adults in the USA currently live with IBD and no cure is available. It is clear that the disease
is complex with influences from host genetics, microbiota and the immune system. Therefore, further
understanding of the interplay between these factors is crucial to developing novel immunotherapies. Previous
mouse models of IBD are limited for studying human disease, entailing the artificial induction of IBD in
susceptible mice. Newer models of spontaneous colitis are necessary to dissect the roles of novel immune
players and their ability to modulate disease and serve as therapeutic targets. Mucosal-associated invariant T
(MAIT) cells are a novel class of innate-like T lymphocytes, highly abundant in human blood and in mucosal
tissues, including the gut. They are potently activated by bacterial-derived metabolites presented by the
evolutionary conserved major histocompatibility complex class I-related molecule, MR1. To date, they have
been implicated in a range of inflammatory diseases. However, their role in IBD and the possible correlations
between their involvement and the course of the disease remains uncertain. Patients with IBD demonstrate
significant infiltration of MAIT cells into inflamed gut tissue and display an inflammatory profile. We have
identified a new inbred mouse strain with high numbers of MAIT cells in primary immune organs and peripheral
tissues, including the colon, compared to other mouse strains analyzed to date. These mice spontaneously
develops pathologic features of colitis that emulate the human disease. We propose to test the hypothesis that
increased MAIT cell numbers in these mice affects their susceptibility to colitis. The objectives of this project
are to establish the interplay of how MAIT cells, microbiota and genetics lead to the development of
spontaneous colitis. In Aim1, we will assess the dynamics of MAIT cell accumulation, activation and gene
expression profile of the gut leukocytes of this new mouse strain as a function of age. In Aim 2, we will
examine the contributions that MAIT cells and/or the microbiota both have towards the development of colitis in
this new mouse strain. These studies will open up new possibilities for understanding the potential role of MAIT
cells in colitis so that it can be exploited for therapeutic usage to improve human health.

## Key facts

- **NIH application ID:** 10436375
- **Project number:** 5R21AI156003-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Laurent Gapin
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $194,375
- **Award type:** 5
- **Project period:** 2021-06-22 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436375

## Citation

> US National Institutes of Health, RePORTER application 10436375, Role of MAIT cells in a mouse model of spontaneous colitis (5R21AI156003-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10436375. Licensed CC0.

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