# Orchestrating intestinal immunity through microbiota-CX3CR1+ cell interactions

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2024 · $531,000

## Abstract

Project Summary
The microbiota provides many key signals that support development and functioning of the immune system.
Interactions between host and microbiota allows for proper induction of immune responses against pathogens.
These interactions are also necessary to limit inflammatory immune responses against the microbiota which, if
left unchecked, will result in inflammatory conditions including inflammatory bowel disease. Many intestinal cell
types including immune cells and the intestinal epithelium recognize and respond to the microbiota. It is unclear
how such signals are integrated to support homeostasis. In humans as well as in animal models of disease,
compositional changes in the microbiota, also known as dysbiosis, correlate with increased susceptibility to
inflammatory disease. Understanding the role of individual microbes within the community would allow for the
development of novel mechanistic approaches to restore homeostasis in the case of inflammatory disease. We
identified a subset of mucosa associated E. coli that induce intestinal macrophage production of IL-1b. This
activates innate protection of the intestinal barrier but also drives proinflammatory T cell responses against these
E. coli. Specific characteristics of these E. coli as well as how they interact with the host immune system likely
drives these responses. In Aim 1 of the proposed work, we will use in vitro and in vivo models to determine how
these E. coli activate IL-1b production. In Aim 2 we will define the regulation and consequence of T cell responses
against these E. coli. Together, these studies will identify molecular crosstalk between intestinal microbes and
immune system that underlie pro-inflammatory responses against the microbiota. Understanding these signals
will allow us to identify mechanisms for regulating these pathways and reducing unnecessary intestinal
inflammation.

## Key facts

- **NIH application ID:** 10911357
- **Project number:** 5R01AI125264-07
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** GRETCHEN E DIEHL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $531,000
- **Award type:** 5
- **Project period:** 2017-03-02 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10911357

## Citation

> US National Institutes of Health, RePORTER application 10911357, Orchestrating intestinal immunity through microbiota-CX3CR1+ cell interactions (5R01AI125264-07). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10911357. Licensed CC0.

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