PGRP3 is a crucial mediator of periodontitis
PGRP3是牙周炎的重要介质
基本信息
- 批准号:10441598
- 负责人:
- 金额:$ 15.4万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-01 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:16S ribosomal RNA sequencingAddressAdultAffectAffinityAlveolar Bone LossAmericanAnti-Inflammatory AgentsAtherosclerosisAttentionAutomobile DrivingBacteriaBindingBiological AssayBiological MarkersBiological ModelsBiologyCell Culture TechniquesCell SeparationCellsChronicClinicalCommunicable DiseasesDataDental PlaqueDevelopmentDiabetes MellitusDiagnosisDiseaseEnvironmentEpithelial CellsEventExhibitsExperimental ModelsFeedbackFinancial HardshipFlow CytometryFluorescent Antibody TechniqueFutureGeneticGenetic PolymorphismGenetic TranscriptionGingivaGingivitisHealthHomeostasisHumanHypertensionImmuneImmune responseImmunohistochemistryImmunologic SurveillanceIn SituIn VitroIndividualInflammationInflammation MediatorsInflammatoryInflammatory ResponseInterferonsKnock-outKnockout MiceKnowledgeLiteratureMediator of activation proteinMicrobeMissionModelingMonitorMucous MembraneNatural Killer CellsOralOrganismOsteolysisPathway interactionsPattern recognition receptorPeriodontitisPopulationPrevalenceProductionProtein IsoformsProteinsPublic HealthRecombinantsRegulationReportingResearchRoleSalivaSamplingSignal TransductionSkinSuspensionsSymbiosisTechniquesTestingTimeTissue SampleTissuesTooth LossUnited States National Institutes of Healthbasechronic inflammatory diseasedesigndisease phenotypedysbiosisexperimental studyfunctional statusgut dysbiosishuman diseasehuman tissueimmunoregulationin vivoinnovationinsightmacrophagemicrobialmicrobial communitymicrobiomemicrobiotamouse modelnovelnovel diagnosticsnovel therapeuticsoral microbiomepeptidoglycan recognition proteinpopulation basedreceptorsingle-cell RNA sequencingskin microbiomesubgingival microbiotatranscriptometranscriptomics
项目摘要
PROJECT SUMMARY
Periodontitis (PD) is one of the most prevalent chronic infectious diseases that causes osteolysis of alveolar
bone and tooth loss. It is estimated that over 47% of the American adult population have some form of PD. In
adults >65, this prevalence increases to >70%, which is three times the prevalence of diabetes, and higher than
that of atherosclerosis or hypertension. The financial burden associated with PD is estimated to be >$10.5
billion/year in the U.S.A alone, and thus require significant attention. Despite several decades of research, the
mechanisms by which the insidious transition from gingivitis to severe forms of PD occurs is poorly understood.
Consequently, there has been little progress in biomarker based diagnosis / monitoring of disease activity, as
well, as in development of new therapeutic options. PGRP3 are novel secreted and soluble receptors that
recognize and respond to bacteria and are emerging as crucial mediators of inflammation. However, their
expression and functional role in PD and the associated dysbiosis remains a critical knowledge gap. Therefore,
the overall objective of this application is to understand the role of PGRP3 in PD and is based on the scientific
premise that, PGRP3 binds to select constituents of the oral microbiome and PGRP3 modulates PD immune
responses. Towards that, this proposal aims to test the central hypothesis PGRP3 selectively targets particular
species found in dysbiotic PD plaque and PGRP3+ cells in PD gingiva exhibit a distinct transcriptome compared
to PGRP3- cells found in the same local environment. The central hypothesis will be tested by pursuing two
specific aims: 1) Identify PGRP3-targeted microbiota in PD and health and characterize the immune response
to them. & 2) Analyze and compare the transcriptomes of PGRP3+ and PGRP3- immune subsets of PD and
healthy gingiva. Under aim 1, bacteria-PGRP3 interactomes will be identified by adapting a novel flow cytometry-
based bacterial cell sorting/16S sequencing assay and the immune response to the highly coating species will
be studied. For the second aim, we will separate the immune subset that we have identified to be PGRP3+ into
PGRP3+ and PGRP- populations through multicolor flow cytometry on gingival single cell suspensions excised
from healthy and PD subjects. We will compare the transcriptomes of the PGRP3+ and PGRP- subsets to
understand their functional role in the local environmental context. These results will be validated with multiplex
immunofluorescence techniques. This research is innovative because it focuses on a never before explored
group of molecules in the oral context and it will involve the adaptation and development of novel techniques
and strategies. The proposed research would be significant as they are expected to provide strong scientific
justification for dissecting the role of PGRP3 in PD dysbiosis and inflammatory dysregulation. Ultimately, such
knowledge would offer new therapeutic and diagnostic options for PD and other inflammatory diseases.
项目总结
项目成果
期刊论文数量(0)
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Sivaraman Prakasam其他文献
Sivaraman Prakasam的其他文献
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