# Immunoregulatory role of PMN leukocytes in periodontitis

> **NIH NIH R21** · UNIVERSITY OF MINNESOTA · 2020 · $231,000

## Abstract

7. PROJECT SUMMARY / ABSTRACT
Periodontitis is a chronic inflammatory disease that is the leading cause of periodontal tissue destruction and
tooth loss. Treating periodontal disease comes at a high economic cost.. Although triggered by a dysbiosis of
the oral microbiota, periodontitis is essentially a disease resulting from a local inflammatory response against a
microbial biofilm surrounding the tooth. The impact of infiltrating neutrophils or neutrophil-like cells on
destructive T cells is unknown. Our current objective is to determine how these cells regulate destructive T
cell responses in a mouse model of chronic periodontitis initiated by Porphyromonas gingivalis (Pg). Activated
neutrophils can express the chemokines CCL2 and CCL20 and may amplify the early inflammatory response
in periodontitis by helping recruit CCL2- and CCL20-responsive Th17 cells to the inflamed gingiva. Current
research has also revealed that neutrophils are not a homogenous group and have different activation states
and functions, which may include suppressive capabilities. So-called polymorphonuclear myeloid-derived
suppressor cells (PMN-MDSCs) in mice are phenotypically and morphologically indistinguishable from regular
neutrophils. However, this subpopulation of PMNs has the ability to actively suppress T cells. Accordingly, we
hypothesize that at initiation of dysbiosis, neutrophils act as positive regulators of Th17 recruitment to the
gingiva and subsequently as negative regulators of local T cell clonal expansion during chronic phases of the
disease. To test this hypothesis we will pursue two specific aims using novel mice strains generated by us.
Aim 1. Determine the potential of CCL2 and CCL20 produced by neutrophils/PMN-MDSCs to recruit
Th17 cells to the oral mucosa during early oral colonization with Pg. We hypothesize that early in Pg-
induced dysbiosis, neutrophils aid recruitment of Th17 cells by boosting gingival levels of CCL2 and CCL20.
To test our hypothesis we will orally infect experimental mice that carry Ccl2 and/or Ccl20 ablations restricted
to neutrophils/PMN-MDSCs with Pg. Mutant mice are expected to recruit fewer Th17 cells to the oral
mucosae and lose less alveolar bone than WT mice after Pg-colonization.
Aim 2. Determine the role of arginase-1 produced by neutrophils/PMN-MDSCs in suppressing
expansion of oral mucosa T cell populations during persistent oral colonization with Pg. We
hypothesize that arginase 1 secreted by PMN-MDSCs or neutrophils suppresses adaptive T cells and innate
γδ T cells late during persistent oral Pg exposure. To test our hypothesis we will orally infect experimental mice
that carry an arg1 ablation restricted to neutrophils/PMN-MDSCs with Pg. We expect mutant mice to have
larger numbers of adaptive T cells and γδ T cells in the oral mucosa and to lose more alveolar bone.
Our proposed research is significant because it will examine novel regulatory roles of neutrophils/PMN-MDSCs
in periodontitis.

## Key facts

- **NIH application ID:** 9873572
- **Project number:** 1R21DE029276-01
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Peter Bittner-Eddy
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $231,000
- **Award type:** 1
- **Project period:** 2020-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9873572

## Citation

> US National Institutes of Health, RePORTER application 9873572, Immunoregulatory role of PMN leukocytes in periodontitis (1R21DE029276-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9873572. Licensed CC0.

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