# Local endogenous regulators of functional immune plasticity in the periodontium

> **NIH NIH R37** · UNIVERSITY OF PENNSYLVANIA · 2020 · $349,500

## Abstract

Project Summary
Periodontitis is a prevalent inflammatory disease that causes destruction of the tooth-supporting tissues
(periodontium). The maintenance of homeostatic mechanisms is essential for protection against inflammatory
damage in the periodontium. In this context, the function of immune cells needs to be tailored according to
specific environmental challenges; for instance, the ability to mount a robust immune response needs to be
followed by timely resolution of inflammation and restoration of tissue integrity. This adaptation is known as
functional immune plasticity and results from an intimate crosstalk of immune cells with tissue-derived factors,
which, in turn, are regulated by and reflect changes of the tissue microenvironment. The functional
characterization of a novel endogenous homeostatic molecule, derived from periodontal tissue-resident cells
and designated developmental endothelial locus-1 (Del-1), has significantly contributed as a prototype
paradigm to the emerging concept that tissues have a “regulatory say” over the host immune response. This
project investigates the overarching hypothesis that Del-1 acts as a local endogenous regulator of functional
immune plasticity by not only regulating periodontal inflammation but also by promoting resolution thereof, and
hence periodontal homeostasis. The proposal comprises three specific aims and focuses on relevant animal
model-based mechanistic and intervention studies, including mice with lineage-specific deletions or
overexpression of Del-1. In Aim 1, it is proposed that Del-1 promotes the resolution of periodontal
inflammation. Aim 2 investigates the mechanism(s) by which Del-1 promotes homeostatic immunity.
Specifically, it is proposed that Del-1 modulates macrophage plasticity via two complementary mechanisms;
inhibition of inflammatory signaling and promotion of a pro-resolution reprogramming of macrophages, both of
which may impact the function of other immune cells, such as T cells. Aim 3 is to determine the importance of
the location of Del-1 expression in the regulation of periodontal inflammation and bone loss. The concept to
establish here is that the cellular source and location of homeostatic molecule expression is functionally
important in that it allows it to perform distinct functions in an appropriate context. This application therefore
offers a fundamentally new insight into the local mechanisms that govern and tailor the function of the immune
system. The proposed research is likely to reveal hitherto unknown mechanisms of immune system plasticity
relevant to the pathogenesis of oral diseases; these mechanisms can be harnessed to develop innovative
approaches to inhibit destructive inflammation and restore tissue integrity.

## Key facts

- **NIH application ID:** 9962367
- **Project number:** 5R37DE026152-05
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Georgios Hajishengallis
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $349,500
- **Award type:** 5
- **Project period:** 2016-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962367

## Citation

> US National Institutes of Health, RePORTER application 9962367, Local endogenous regulators of functional immune plasticity in the periodontium (5R37DE026152-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9962367. Licensed CC0.

---

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