# Mechanisms of Mucosal Th17 Cell Induction By Segmented Filamentous Bacteria

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $582,920

## Abstract

How resident gut bacteria engage adaptive immunity is not clear. Commensal specific T cells are difficult
to detect in the LP and multiple mechanisms have been described that prevent development of such
cells at steady state. These include sequestration in the lumen and immunological ignorance, re-direction
of commensal-specific T cells into the Treg compartment, and negative selection by type 3 innate
lymphoide cells (ILC3). We have identified an example of commensal-host interaction in which
segmented filamentous bacteria (SFB) induce an antigen-specific non-inflammatory Th17 cell response.
Therefore, certain commensals do engage adaptive immunity and generate effector T cells that are
apparently non-inflammatory. The mechanisms involved in this process are not known, but are of
significant interest, because they may help design strategies to curb inflammatory potential of effector T
cells, while preserving their effector function. We also showed that this process occurs through a unique
antigen-presentation pathway that requires intestinal macrophages (Mfs). Here we propose to investigate
the mechanistic role of intestinal Mfs as well as the pathogenicity of the induced Th17 cells. We also
show that intestinal epithelial cells are involved in the crosstalk between the bacteria and Mfs, and will
investigate a novel potential mechanism of this interaction. We will investigate the following specific aims:
1) we will identify the innate immune subset presenting SFB antigens; 2) we will characterize the co-
operative role of intestinal epithelial cells, Mfs and dendritic cells in generating Th17 cells; 3) we will
investigate the pathogenicity of the generated Th17 cells and identify genes that regulate their ability to
cause inflammation; 4) we will examine whether a similar antigen-presentation pathway is involved in
induction of Th17 cells by human commensal bacteria.

## Key facts

- **NIH application ID:** 9990771
- **Project number:** 5R01DK098378-08
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Ivaylo Ivanov Ivanov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $582,920
- **Award type:** 5
- **Project period:** 2013-04-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9990771

## Citation

> US National Institutes of Health, RePORTER application 9990771, Mechanisms of Mucosal Th17 Cell Induction By Segmented Filamentous Bacteria (5R01DK098378-08). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9990771. Licensed CC0.

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