# Dendritic Cells and Periodontal Disease

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $382,375

## Abstract

Project Summary
In the initial funding period of this award we provided conclusive evidence that dendritic cells play a central
role in the pathogenesis of periodontal disease and that this function is modulated through FOXO1 and Akt1.
Contrary to our expectations, lineage specific FOXO1 deletion in dendritic cells significantly increased
susceptibility to periodontitis whereas the opposite result occurred when Akt1 was deleted in dendritic cells.
DC-specific Akt1 deletion blocked bacteria-induced periodontitis whereas DC-specific FOXO1 deletion
increased it. These exciting results provide the first concrete evidence that DC play an instrumental role in
modulating susceptibility to periodontitis and suggest a mechanism through Akt1 and FOXO1. Dendritic cells
have multiple functions that can affect periodontal inflammation and bone loss. They may produce factors
that may favor the formation of T regs, which have been shown to reduce periodontal breakdown. They also
can direct the production of an antibody response that is potentially protective. Alternatively, DCs can
transdifferentiate to osteoclasts, effector cells responsible for bone resorption. We will examine each of these
three potential mechanisms through which the FOXO1 and Akt1 May regulate DC to control susceptibility to
periodontitis. We propose three mechanisms by which FOXO1/Akt1 can modulate susceptibility to
periodontitis. These mechanisms are compatible with each other and all three could potentially play a role.
The experiments involve an in vivo experimental model of P gingivalis and F nucleatum induced periodontitis
in mice with lineage specific FOXO1 or Akt1 deletion in DC along with companion in vitro studies. The goal
of Aim 1 is to establish mechanisms through which FOXO1 in dendritic cells modulates periodontal disease
susceptibility, while the goal of Aim 2 is to establish mechanisms through which Akt1 has the opposite effect.
Three compatible mechanisms will be investigated, modulation of the adaptive immune response by altering
Treg/Th2 versus Th1/Th17 responses, alteration of an antibody response that confers protection against
periodontal breakdown, and transdifferentiation of immature DC to osteoclasts.

## Key facts

- **NIH application ID:** 9969077
- **Project number:** 5R01DE021921-08
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** DANA T GRAVES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $382,375
- **Award type:** 5
- **Project period:** 2012-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9969077

## Citation

> US National Institutes of Health, RePORTER application 9969077, Dendritic Cells and Periodontal Disease (5R01DE021921-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9969077. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*