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Assessing the role of Type I Interferon (IFN-I) in Periodontal Disease

Award Number: R01DE032307
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2023
PERIOD OF PERFORMANCE END DATE: 12/31/2027

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Assessing the role of Type I Interferon (IFN-I) in Periodontal Disease - Project Summary Periodontitis, which results in irreversible damage in hard and soft tooth-supporting tissues, affects 42% US adults. This extremely prevalent inflammatory oral disease is also tightly associated with systemic diseases such as diabetes. Clinical studies have shown that periodontitis contains mixed disease phenotypes. For example, the disease progression pattern in about 20% of periodontitis patients is clearly distinct from that of the majority in a population. Recently, we used a data-driven approach to create a periodontal profile classification (PPC)-Staging system by integrating periodontal measurements and indices from a closely followed up community cohort. After validation, we demonstrated that this new PPC-Staging tool has drastically improved clinical associations with several systemic diseases including diabetes, stroke, and coronary heart disease due to the improved homogeneity of each PPC-Stage (I to VII). Through a proteomic biomarker analysis in the gingival crevicular fluid of a patient pool from the cohort, we found that the expression pattern of the interferon-β (IFN-β) cytokine, a classical member of type I interferon (IFN-I), in PPC-Stages mimics that of interleukin-1 receptor antagonist (IL-1RA), a well-described classical anti-inflammatory cytokine. This novel finding prompted us to evaluate the role of IFN-I in periodontitis. Using a mouse periodontitis model, we found that IFN-I plays a protective role in alveolar bone loss. We further found that such a protective role of IFN-I is associated with a dampening of an interleukin (IL)-17-neutropphil axis, while the transcription of Il27 in local gingiva was upregulated. The role of IL-27 in an integral IFN-I pathway has yet remained to be elucidated in periodontitis. We further showed that IFN-β signaling suppressed the lipopolysaccharide-induced proinflammatory cytokine production in and potently inhibited osteoclast differentiation from bone marrow- derived monocytes. We therefore hypothesize that an integral IFN-I response in monocytic lineage plays a protective role in periodontitis by deactivating an IL-17-neurophil axis through an IL-27 pathway. We seek to gain insight into the mechanism of IFN-I in modulating innate and adaptive immune responses in periodontal disease. We propose to test this central hypothesis by the following approaches: 1) we will first define the role of Type I IFN- IL-27 pathway in IL-17-neutrophil axis using the animal periodontitis model; 2) we will then assess the specific role of IFN-I signaling in myeloid lineage that contains monocytic /osteoclast precursor cells in the periodontitis model; 3) we will also evaluate the effect of a locally delivered novel nanoparticle-mediated sustained release of IFN-β/IFN-I stimulator in the periodontitis model. Our goal of this project is to advance the understanding of INF-I, a clinically relevant yet under-investigated molecule, in periodontal disease, and to leverage IFN-β or IFN-I-centered inflammatory networks as biomarkers to further refine the clinical periodontal disease classification. In addition, this research proposal will provide evidence to target IFN-Is as an adjunctive therapeutic measure in a subset of patients to improve precision periodontal health.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $388,750 )
2025	2025	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Oral Diseases and Disorders Research	001	3	5/5/2025	NON-COMPETING CONTINUATION	$38,875
2025	2025	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Oral Diseases and Disorders Research	000	3	12/10/2024	NON-COMPETING CONTINUATION	$349,875
														Subtotal = $388,750

Issue Date FY: 2024 ( Subtotal = $380,975 )
2024	2024	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Oral Diseases and Disorders Research	001	2	6/10/2024	NON-COMPETING CONTINUATION	$31,100
2024	2024	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Oral Diseases and Disorders Research	000	2	11/20/2023	NON-COMPETING CONTINUATION	$349,875
														Subtotal = $380,975

Issue Date FY: 2023 ( Subtotal = $388,750 )
2023	2023	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Oral Diseases and Disorders Research	000	1	12/26/2022	NEW	$388,750
														Subtotal = $388,750

Grand Total All Awards = $1,158,475

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Assessing the role of Type I Interferon (IFN-I) in Periodontal Disease

Award Number: R01DE032307

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 01/01/2023

PERIOD OF PERFORMANCE END DATE: 12/31/2027

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