# Microbiome and immunosenescence of  T cells repertoire

> **NIH NIH R01** · GEORGIA STATE UNIVERSITY · 2022 · $390,000

## Abstract

The intestinal microbiota is a major contributor of antigens recognized by intestinal CD4 T
cells. How these antigens influence CD4 T cells immunosenescence and their effector functions
in old mice and humans remains unclear. Therefore, there is a need to develop a standardized
microbial flora that has a manageable size and resembles natural microbiome that when
administered to old, frail individuals will rebalance their intestinal homeostasis. The goal of this
proposal is to test if this new oligoclonal collection of mouse intestinal commensals (oligo-MM),
designed by system and genome-based approaches to recapitulate complete microbiome can
help revitalize an aging immune system. In particular, we will investigate how oligo-MM microbiota
and its main component Akkermasia municiphila interacts with Cd4 T cells and discover immune
epitopes that these cells recognize from this bacteria. In Aim 1 we will investigate how specific
intestinal commensals influence activation and repertoire of CD4 T cells in old mice. In our Aim 2
we will demonstrate that A. municiphila derived antigens induce naïve CD4Foxp3- T cells
conversion to CD4Foxp3+ pTregs and substantially increase the number of these cells in old mice.
We hypothesize that the therapeutic administration of A. municiphila to old mice can improve
tolerance to intestinal microbiota and reduce immunosenescence. Overall this research will help
develop new strategies based on strictly controlled microbiota-based therapies to control intestinal
inflammation in elderly.

## Key facts

- **NIH application ID:** 10417234
- **Project number:** 5R01AG068875-03
- **Recipient organization:** GEORGIA STATE UNIVERSITY
- **Principal Investigator:** LESZEK IGNATOWICZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $390,000
- **Award type:** 5
- **Project period:** 2020-09-30 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10417234

## Citation

> US National Institutes of Health, RePORTER application 10417234, Microbiome and immunosenescence of  T cells repertoire (5R01AG068875-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10417234. Licensed CC0.

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