# Differential Regulation of T Cell Responses to the Commensal Bacterium Akkermansia Muciniphila

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA BERKELEY · 2022 · $43,462

## Abstract

Project Summary
 The intestines are inhabited by a complex community of commensal bacteria known as the microbiota,
which play a fundamental role in shaping host physiology and immune function. In general, T cells remain
ignorant of commensal bacterial antigens, or adopt a regulatory fate if activated. However, a small number of
commensal bacterial antigens have been identified that elicit effector T cell responses. Such commensal-
reactive T cells can alter how the immune system responds to local challenges, such as intestinal pathogens.
Notably, commensal-reactive T cells have also been shown to influence how the immune system responds in
other contexts, such as during autoimmune disease and cancer.
 This application focuses on the commensal bacterial species Akkermansia muciniphila, which colonizes
both healthy mice and humans. The presence of A. muciniphila in the intestines has been linked with changes
in host immune function, and protection against a number of disease states, although the mechanisms
underlying these effects are unclear. The Barton lab has developed powerful tools for tracking the T cell
response to A. muciniphila. They recently used these tools to demonstrate that A. muciniphila induces a unique
context-dependent T cell response unlike what has been described for other commensal species. In
gnotobiotic mice with a minimal microbiota, A. muciniphila elicits a defined T follicular helper cell response;
however, in mice with a more complex SPF microbiota, this bacterium elicits helper T cells with multiple
effector phenotypes. These results suggest that the immune response to A. muciniphila is variable and
depends on cues other than the presence or absence of the bacteria.
 Our goal is to understand the mechanisms by which A. muciniphila induces specific types of T cell
responses, as well as the implications for host health of altering the anti-commensal immune response. In Aim
1, we will examine the immune response to A. muciniphila in the setting of several defined microbial
communities in order to examine how additional commensal species alter the A. muciniphila-specific T cell
response. In Aim 2, we will characterize the APCs responsible for presenting A. muciniphila antigens in
contexts in which the T cell response to A. muciniphila is varied. Finally, in Aim 3, we will examine how
changes in the nature of the A. muciniphila-specific T cell response impact host health. Together, these studies
will provide mechanistic insight into how the immune system responds to the microbiota and how immune
responses to commensal bacteria can alter host physiology.

## Key facts

- **NIH application ID:** 10356844
- **Project number:** 5F31AI161893-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Shaina L Carroll
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $43,462
- **Award type:** 5
- **Project period:** 2021-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10356844

## Citation

> US National Institutes of Health, RePORTER application 10356844, Differential Regulation of T Cell Responses to the Commensal Bacterium Akkermansia Muciniphila (5F31AI161893-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10356844. Licensed CC0.

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