# IL-22, Immune Plasticity, and Autotherapy in the Periodontium

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2022 · $382,078

## Abstract

Project Summary
Robustness is the ability of a system to maintain its functionality against internal or external perturbations and is
enabled by mechanisms of plasticity, a major feature of biological systems such as the immune system.
Autotherapies are approaches to optimize endogenous tissue responses to maintain health, treat diseases and
enhance tissue repair, in great part by restoring biological robustness. Interleukin (IL)-22 mediates unidirectional
communication from immune cells to tissue stromal cells and promotes homeostatic immunity, stem cell function
and tissue regeneration. However, IL-22 is associated with both detrimental and protective activities in chronic
inflammatory disorders, which has confounded its potential as a therapeutic target. The overall objective of this
proposal is to clearly define the functions of IL-22 in periodontal disease (PD) and attain a context-dependent
understanding of its protective or destructive potential, which will enable IL-22-targeted autotherapies to promote
immune robustness in the periodontium. The overall hypothesis is that IL-22 acts in a context-dependent manner
that influences the plasticity of the tissue from one tailored to perform immune surveillance or fight infections, to
one fitted for regeneration. Specifically, IL-22 is proposed to regulate periodontal tissue immune plasticity by (i)
preserving tissue integrity during steady-state (examined in Aim 1), contributing to vigorous immune responses
that become destructive during PD (Aim 2), and acting as an effector of bone regeneration in the resolution
phase (Aim 3). In Aim 1, in vivo intervention studies were designed to explore the requirement for IL-22 in
periodontal tissue homeostasis at steady state. Aim 2 examines, through both in vitro and in vivo mechanistic
experiments, the hypothesis that IL-22 synergizes with IL-17, a proinflammatory cytokine that is upregulated in
PD, to promote destructive inflammation during the inductive phase of PD. Aim 3 explores the hypothesis that
IL-22 promotes inflammation clearance and bone regeneration during the resolution phase of PD, when the
expression of IL-17 massively declines. Regarding the mechanism by which IL-22 can promote osteogenesis, it
will be investigated whether IL-22 promotes the proliferation and osteogenic differentiation of mesenchymal stem
cells. The proposed studies are expected to lead to a context-dependent understanding of the biological
functions of IL-22 in PD, leading to novel IL-22-targeted autotherapies to appropriately modulate immune
plasticity and restore homeostasis in the periodontium, thereby benefiting PD patients.

## Key facts

- **NIH application ID:** 10369593
- **Project number:** 5R01DE029436-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Georgios Hajishengallis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $382,078
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10369593

## Citation

> US National Institutes of Health, RePORTER application 10369593, IL-22, Immune Plasticity, and Autotherapy in the Periodontium (5R01DE029436-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10369593. Licensed CC0.

---

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